DOSAGE FORMS AND DRUG DELIVERY application (NDA) and

SYSTEMS approval of the FDA.

Klint Jun Ganancial ○ It became the responsibility of
Joyce G. Canete the FDA to either grant or
deny permission to
PHARMACEUTICS manufacture and distribute a
● Used in pharmacy and the new product.
pharmaceutical sciences to
encompass a wide range of subject DURHAM-HUMPHREY AMENDMENT OF
areas that are all associated with the 1952
steps to which a drug is subjected OVER THE COUNTER (OTC) OR
towards the end of its development. NONPRESCRIPTION DRUGS
○ It encompasses the stages that ● Drugs deemed safe enough for use by
follow on from the discovery or the layman in the self-treatment of
synthesis of the drug, its simple conditions for which competent
isolation and purification, and medical care is not sought
its testing for beneficial ● may be sold without a physician's or
pharmacological effects and other legally authorized prescriber’s
absence of serious toxicological prescription.
problems.
● “Pharmaceutics converts a drug PRESCRIPTION DRUGS (Legend drugs)
into medicine” ● Drugs that are considered useful only
*medicine = drug in its final dosage after expert diagnosis or too
form dangerous for use in self-medication
● Made available to the patient only by
DRUG REGULATION AND CONTROL prescription.
● Bear the symbol “Rx Only” or the
THE FEDERAL FOOD, DRUG, AND legend
COSMETIC ACT OF 1938 ● “Caution: Federal Law Prohibits
● SULFANILAMIDE (Antibacterial) Dispensing Without Prescription.”
○ Popular antibacterial drug for
pediatrics *Ex. Naproxen 275 mg - Nonprescription drug;
○ Alcohol based Naproxen 500 mg - prescription drug
○ Elixir (Preparation) Mefenamic acid: 250 mg nonprescription drug;
● DIETHYLENE GLYCOL 500 mg prescription drug
○ Antifreeze KEFAUVER-HARRIS AMENDMENTS OF
○ Solvent 1962 *Safety
● Necessity for proper product ● A tragedy in 1960 led to its passage
formulation and thorough ● New synthetic drug, thalidomide
pharmacologic and toxicologic (used for morning sickness),
testing of the therapeutic agent and recommended as a sedative and
pharmaceutical ingredients. tranquilizer, was being sold OTC in
Europe.
● Creation of the FDA ● Thalidomide given to women during
○ to administer and enforce pregnancy produced birth defects,
FD&C ACT of 1938 most notably phocomelia
○ The 1938 act prohibits the ● The purpose of the enactment was to
distribution and use of any new ensure a greater degree of safety for
drug or drug product without approved drugs.
the prior filing of a new drug ○ New drug is required to file an
investigational new-drug
 application (IND) with the FDA psychologic or
before the drug may be physical
clinically tested on human dependence
subjects
SCHEDULE IV Drugs with Specified
accepted quantities of
COMPREHENSIVE DRUG ABUSE medical uses difenoxin,
PREVENTION AND CONTROL ACT OF 1970 and low diazepam,
● served to consolidate and codify potential for oxazepam, and
control authority over drugs of abuse abuse relative to similar agents.
those in
into a single statute. Schedule III that
○ Administered by the Drug if abused may
Enforcement Administration lead to
(DEA) in the Department of moderate
Justice physiologic and
physical
● established five “schedules” for the dependence.
classification and control of drug
substances that are subject to abuse. SCHEDULE V Drugs with Specified
● schedules provide for decreasing accepted quantities of
levels of control, from schedule I to medical uses dihydrocodeine,
and low hydrocodone,
schedule V. potential for and similar
● Basis for RA 9165 in the Philippines abuse relative agents
to those in
schedule IV that
SCHEDULE DESCRIPTION EXAMPLES if abused may
lead to limited
physical
SCHEDULE I Drugs with no Heroin, LSD, dependence or
accepted mescaline, psychologic
medical use, or peyote, dependence
other methaqualone, relative to drugs
substances with marijuana in schedule IV.
a high potential
for abuse *refer to R.A. 9165 for the examples

SCHEDULE II Drugs with Morphine, FDA PREGNANCY CATEGORIES

accepted cocaine,
medical uses methamphetami
● The FDA has established five
and a high ne, amobarbital categories that can be used to
potential for estimate the potential of a
abuse that if systemically absorbed drug for
abused may causing birth defects.
lead to severe
psychological ● The Pregnancy Category “X” is the
or physical strongest and states that if any data
dependence exists that a drug may be implicated as
a teratogen and the risk versus benefit
SCHEDULE III Drugs with Specified ratio does not support the use of the
accepted quantities of
medical uses codeine, drug, then the drug is
and a potential hydrocodone contraindicated during pregnancy.
for abuse less and similar
than those listed agents
in schedules I FDA PHARMACEUTICAL PREGNANCY CATEGORIES
and II that if
abused may Category A Adequate and well-controlled
lead to human studies demonstrate no
moderate risk.
 Category B Animal studies demonstrate no adverse health consequences.
risk, but no human studies have *X integrity/quality
been performed. OR Animal *most common
studies demonstrate a risk, but Ex. packaging, wrong label
human studies have
demonstrated no risk.
New Drug Development and Approval
Category C Animal studies demonstrate a Process
risk, but no human studies have *Pre-clinical - compound is isolated;
been performed. Potential
benefits may outweigh the risks.
physico-chemical properties of drug or
compound is known
Category D Human studies demonstrate a *Phase IV - second pharmacological action of
risk. Potential benefits may a drug can be discovered
outweigh the risks.

Category X Animal or human studies

GOAL DRUG VS LEAD COMPOUND VS
demonstrate a risk. The PRODRUG VS ORPHAN DRUG
risks outweigh the potential
benefits. GOAL DRUG
A goal drug would:
PRODUCT RECALL
DRUG PRODUCT RECALL
● If the FDA or a manufacturer finds that
a marketed product presents a threat
or a potential threat to consumer
safety, that product may be recalled or
sought for return to the manufacturer
from its depth of distribution.
● Reported problems may include
product defects, product
adulteration, container leakage,
improper labeling, unexpected ● Produce the specifically desired effect
adverse reactions, and others. ● Be administered by the most desired
route (generally orally)
*most convenient route
PRODUCT
RECALL
DESCRIPTION ● Minimal dosage and dosing frequency
CLASSIFICATION *longer duration of action
● Have optimal onset and duration of
CLASS I There is a reasonable probability
that the use of or exposure to a
activity
violative product will cause serious *longer duration of activity, lesser
adverse health consequences or dosing frequency
death ● Exhibit no side effects
Ex. wrong label, defective device ● Following its desired effect would be
CLASS II The use of or exposure to a violative
eliminated from the body efficiently,
product may cause temporary or completely, and without residual effect.
medically reversible adverse ● Easily produced at low cost
health consequences or the = lower price
probability of serious adverse health
● Pharmaceutically elegant
consequences are remote.
Ex. patient experienced severe ● Physically and chemically stable in
diarrhea (reversible) various conditions of use and storage
*less production cost
CLASS III The use of or exposure to a violative
product is not likely to cause
LEAD COMPOUND
 ● A prototype chemical compound that
has a fundamental desired biologic
or pharmacologic activity.
*usually discovered from plants
(metabolites)
● Active: may not possess all of the
features desired, such as potency,
absorbability, solubility, low toxicity, and
so forth.
○ modify the lead compound’s
chemical structure to achieve
the desired features while
reducing the undesired ones PRODRUG ACTIVE DRUG
● Example:
Protonsil Sulfanilamide

Levodopa Dopamine

Talampicillin Ampicillin

Diazepam Oxazepam

Azathioprine Mercaptopurine

Cortisone Hydrocortisone
Zaprinast (problems with specificity and
solubility) → Pyrazolopyrimidinone → Prednisone Prednisolone
Sildenafil citrate (ANTIHYPERTENSIVE;
Enalapril Enalaprilat
vasodilator, tx for erectile dysfunction - second
pharmacological activity)
*minoxidil: was originally used for treating ORPHAN DRUG
high blood pressure; secondary use: hair ● ORPHAN DISEASE is defined as a
regrower due to its side effect “Hirsutism” rare disease or condition that
affects fewer than 200,000 people in
the United States and for which there
PRODRUG is no reasonable expectation that
● used to describe a compound that costs of research and development for
requires metabolic biotransformation the indication can be recovered by
after administration to produce the sales of the product in the United
desired pharmacologically active States
compound. ○ FDA provides support grants to
● Inactive Prodrug Biotransformation → Active conduct clinical trials on safety
Compound and effectiveness
● Example: Enalapril maleate ○ A 7-year period of exclusive
------(Hydrolysis)------> Enalaprilat (active marketing rights after regulatory
compound) approval of a product.

CLINICAL TRIALS
Investigational New Drug Application (IND)
● Submission
● FDA Review
PRODRUG: EXAMPLES Clinical Trials
 ● Phase I macodynam
● Phase II ic,interactio
● Phase III ns

PHASE I II Up to Several First studies 45%

several months in patients:
● SAFETY hundred to 2 safety and
● Investigational New Drug application years efficacy.
IND → proceed to Phase I
● 20 - 100 healthy volunteers take drug III Several 1-4 Definitive 5-10%
for about one month hundred years studies in
to patients;
● Information Learned several safety and
1. Absorption and metabolism thousand efficacy
2. Effects on organs and tissue
3. Side effects as dosage is
PHASE 4 STUDIES AND POSTMARKETING
increased
SURVEILLANCE
PHASE II
● Contribute to the understanding of the
● EFFECTIVENESS
drug’s mechanism or scope of action,
● Several hundred health-impaired
may indicate possible new
patients
therapeutic uses for the drug, and/ or
● Composed of:
may demonstrate the need for
○ Treatment Group
additional dosage strengths, dosage
○ Control Group
forms, or routes of administration.
● Information Learned
● Postmarketing studies may also reveal
1. Effectiveness in treating
additional side effects, serious and
disease
unexpected adverse effects, and/or
2. Short-term side effects in
drug interactions
health-impaired patients
3. Dose range
PACKAGING AND STORAGE OF
PHASE III
PHARMACEUTICALS
● SAFETY, EFFECTIVENESS,
CONTAINERS
DOSAGE
According To USP:
● Hundreds or thousands of
● CONTAINER
health-impaired patients
○ “that which holds the article
● Information Learned
and is or may be in direct
1. Benefit/risk relationship of drug
contact with the article.”
2. Less common and longer term
side effects
● IMMEDIATE CONTAINER
3. Labeling information
○ “that which is in direct contact
with the article at all times.”
Summary:
○ Closure, blister foils, bottles
Phase No. of Length Purpose % of (ensure compatibility)
patients drugs
succes
sfully ● SINGLE-DOSE CONTAINER
complet ○ is one that holds a quantity of
ing* drug intended as a single dose
and when opened, cannot be
I 20-100 Several First studies 67%
months in mean:
resealed with assurance that
tolerability, sterility has been maintained.
pharmacoki ○ Example: ampule
netics,phar ● MULTIPLE-DOSE CONTAINER
 ○ is a hermetic container that
II Treated soda lime glass
permits withdrawal of
successive portions of the III Soda lime glass
contents without changing the
strength or endangering the NP General purpose soda lime glass
quality or purity of the
remaining portion.*
○ Example: multiple dose vials ● Water Attack Test - measures the
which contain bacteriostatic amount of alkali released from the
agents which can prevent the glass in the specified test conditions.
growth of microorganisms after *parenteral
successive withdrawal of doses
PLASTIC CONTAINERS
According to their ability to protect their DIFFERENT TYPES OF PLASTIC
contents from external conditions: ● PVC (polyvinyl chloride)
● HERMETIC CONTAINER ○ Rigid (to protect product from
○ is impervious to air or any external stress), good clarity
other gas under the ordinary or but unsuitable for gamma
customary conditions of sterilization.
handling, shipment, storage, *Terminal sterilization - process of sterilizing a
and distribution. product in its final container
○ Provides the highest protection ● PET (polyethylene terephthalate)
to the product ○ Usually used in mineral water
bottles and other galenical
preparations
● TIGHT CONTAINER ● APET (amorphous polyethylene
○ Protects the contents from terephthalate)
contamination by extraneous ● PETG (polyethylene terephthalate
liquids, solids or vapors; and glycol)
from efflorescence, ○ APET & PETG have excellent
deliquescence, or evaporation transparency and luster and
under the ordinary or can be sterilized with gamma
customary conditions of radiation
handling, shipment, storage, ○ *Used in packaging sterile
and distribution and is capable preparations
of tight reclosure. DRUG-PLASTIC CONSIDERATION
● WELL-CLOSED CONTAINER
○ It protect the contents from
extraneous solids and from
and from loss of the article
under ordinary conditions of
handling, shipment, storage
and distribution.
○ Least protective

GLASS TYPES
TYPE GENERAL DESCRIPTION

I Highly resistant borosilicate glass

*Leaching - components of the container goes Oral contraceptive compact: earliest
into the product (e.g. Bottled water left inside packages developed to assist adherence to a
the car) prescribed dosing schedule.
*Adsorption - components of the formulation
are adsorb on the “surface of the container”
(problem: overdose)
*Absorption - absorb “into the container”
(problem: underdose)

CHILD-RESISTANT PACKAGING
CHILD-RESISTANT CONTAINER: TAMPER-EVIDENT PACKAGING
● is defined as one that is significantly ● A tamper-evident package is defined
difficult for children under 5 years of as “one having one or more indicators
age to open or to obtain a harmful or barriers to entry which, if breached
amount of its contents within a or missing, can reasonably be
reasonable time and that is not difficult expected to provide visible evidence
for “normal adults” to use properly. to consumers that tampering has
● 4 BASIC DESIGNS occurred.”
1. Align the arrows ● The indicators or barriers may involve
2. Press down and turn - common the immediate drug product container
in pill bottles in US and/or an outer container or carton.
3. Squeeze and turn -
suspensions
4. Latch top PACKAGE TYPE TAMPER PROTECTION

FILM WRAPPER Sealed around product and/or

COMPLIANCE PACKAGING product container; film must be
FACTORS associated with cut or torn to remove product
non-compliance:
● Misunderstanding the dosing schedule BLISTER/ Individually sealed dose units;
● Confusion STRIP PACK removal requires tearing or
○ multiple medications breaking individual
(associated with geriatric compartment
patients)
● Forgetfulness (associated with geriatric BUBBLE PACK Product and container sealed
in plastic, usually mounted on
patients)
display card; plastic must be
● Premature discontinue cut or broken open to remove
○ feeling of well being product
○ Example: antibacterial agents
SHRINK SEAL, Shrunk by heat or drying to
Example of compliance packaging: BAND OR conform to cap; must be torn to
WRAPPERS open package
(commonly found in bottles)

FOIL, PAPER OR Sealed individual packet; must

PLASTIC be torn to reach product
POUNCH *For antibacterial products
which are photosensitive
*Example: co-amoxiclav
BOTTLE SEAL Paper or foil sealed to mouth
STORAGE
of container under cap; must ● To ensure the stability of a
be torn or broken to reach pharmaceutical
product ● preparation for the period of its
*usually in 30s or 100s bottles intended shelf life, the product must
be stored in proper conditions.
TAPE SEALS Paper or foil sealed over ● The labeling of each product includes
carton flap or bottle cap; must the desired conditions of storage.
be torn or broken to reach ● The terms generally employed in such
product
labeling have meanings defined by the
BREAKABLE Plastic or metal tearaway cap USP
CAP over container; must be broken
to remove TERM DESCRIPTION
SEALED TUBE Seal over mouth of tube; must COLD ● Any temperature not
be punctured to reach product exceeding 8°C (46°F).
● REFRIGERATOR: 2° to 8°C
SEALED Carton flaps sealed; carton (36° and 46°F)
CARTON cannot be opened without ● FREEZER: −25° to −10°C
damage (−13° and 14°F)
AEROSOL Tamper-resistant by design COOL 8° to 15°C (46°and 59°F).
CONTAINER
An article for which storage in a cool
place is directed may alternatively
be stored in a refrigerator unless
otherwise specified in the individual
monograph

ROOM The temperature prevailing in a

TEMPERAT
working area. 20° to 25°C (68° to
URE
77°F)
Allows for temperature variations
between 15°C and 30°C (59° and
86°F)

WARM 30° to 40°C (86°and 104°F).

TAMPER EVIDENT PACKAGING: Maximum allowed temperature for

Safety Seals: the shrink-wrap plastic must be drugstores in the Philippines: 30°C
torn off and removed to open the container. EXCESSIVE Above 40°C (104°F).
Twist and Break caps: the cap separates into HEAT
two pieces after it has been opened.
Blister-packs: foil and paper backing must be
cut or peeled off to access tablets. FLAVORING PHARMACEUTICALS
Safety stickers: a sticker connects the cap to ● The addition of flavoring agents to
the bottle and is broken when the bottle is liquid medication can mask the
opened. disagreeable taste.
Foil seals: underneath the cap, a layer of foil
must be removed to access contents. FLAVOR DESCRIPTION

NATURAL In “all natural” flavors, one doesn’t

FLAVOR necessarily know the exact
 chemical composition. May only have to declare in
ingredient declaration.
EXAMPLE: fruit or fruit juice

ARTIFICIAL Any substance used to impart FLAVORS CONCENTRATIONS

FLAVOR flavor that is not derived from a
WATER-SOLUBLE Generally start at 0.2% for
spice, fruit or fruit juice, vegetable
FLAVORS artificial and 1%–2% for
or vegetable juice, edible yeast, natural flavors.
herb, bark, bud, root, leaf or similar
plant material, meat, fish, poultry, OIL-SOLUBLE Generally start at 0.1% in
eggs, dairy products, or FLAVORS finished products for artificial
fermentation products thereof. flavors and 0.2% for natural
flavors.
*exact composition is known
POWDERED Generally start at 0.1% in
SPICE Any aromatic vegetable substance FLAVORS finished product for
(more in whole, broken, or ground form, artificial flavors and 0.75% for
natural flavors.
encountered except substances traditionally
in the food regarded as foods, such as onions, *artificial flavors usually require only a small
industry) garlic, and celery; whose amount
significant function in food is
seasoning rather than nutritional; SWEETENING PHARMACEUTICALS
that is true to name; and from
which no portion of any volatile oil
or other flavoring principle has ARTIFICIAL PROPERTIES
been removed SWEETENER

SACCHARIN Excreted by the kidneys virtually

unchanged.
COMMERCIAL DESCRIPTION
300 times as sweet as sucrose
FLAVOR
Warning labels be used to advise
Natural ABCD All components derived from
consumers that saccharin caused
flavor ABCD.
cancer in animals
ABCD flavor, At least one component and
CYCLAMATE metabolized, or processed, in the
natural artificial-derived from ABCD.
digestive tract, and its by-products
are excreted by the kidneys.
No definition of natural to
artificial
ASPARTAME breaks down in the body into three
basic components: the amino acids
ABCD flavor, WONF All components natural.
phenylalanine and aspartic acid,
(With One Natural
and methanol.
Flavor) At least one component derived
from ABCD.
Contraindicated: PKU
(Phenylketonuria)
Natural flavor, All components are natural.
ABCD *Side effect: mental retardation
type No components derived from *popular in litro packs
ABCD.
ACESULFAME Structurally similar to saccharin; 130
ABCD flavor, All components are artificial. POTASSIUM times as sweet as sucrose
artificial
Excreted unchanged in the urine
Conceptual flavors May contain artificial flavors.
STEVIA extract from the leaves of the plant
No reference point. Stevia rebaudiana bertoni.
 It is natural, non toxic and safe 30 ● extensively use in foods, drugs, and
times as sweet as cane sugar, or cosmetics.
sucrose. ● Researchers in Russia reported that
this color, caused cancer in rats.
It can be used in both hot and cold
preparations.
● FDA investigations and a series of
tests that eventually resulted in
withdrawal of FD&C Red No. 2 from
COLORING PHARMACEUTICALS the FDA certified list in 1976 because
● FOR AESTHETICS its sponsors were unable to prove
● COAL TAR (pix carbonis) safety.
○ thick black viscid liquid
○ by product of destructive FD&C Red No. 4
distillation of coal. ● Approval terminated because of
○ source of synthetic coloring unresolved safety questions.
agents in pharm. products in ● Use in maraschino cherries and
the middle of the 19th century ingested drugs
● Dyes ● FD&C Red No. 4 is now permitted only
○ added to pharmaceutical in externally
preparations in the form of ● applied drugs and cosmetics.
diluted solutions
● Lakes FD&C Yellow No. 5
○ Pigment consisting of a ● Also known as TARTRAZINE
substratum of alumina hydrate ● causes allergic-type reactions in
on which the dye or many people.
precipitated. ● People who are allergic to Aspirin are
○ commonly used in the form of also likely to be allergic to this dye.
fine dispersions or ● FDA requires listing of this dye by
suspensions. name on the labels of foods (e.g.,
ANILINE: butter, cheese, ice cream, NOVA
● Derivative of benzene chips) and ingested drugs containing it.
● Colorless
● Where 90% of the dyes used in the PRESERVATIVES
products are synthesized ● Preparations that provide excellent
● FDA - regulates use color additives growth media for microbes
in foods, drugs, and cosmetics ○ AQUEOUS PREPARATIONS:
(Federal Food, Drug, and Cosmetic Act syrups, emulsions, suspensions
of 1938) ○ SEMI SOLID PREPARATIONS
particularly creams.
FD&C food, drugs and cosmetics ● HYDRO-ALCOHOLIC & MOST
ADDITIVES ALCOHOLIC PREPARATION
○ may not require addition of
D&C drugs, some in cosmetics & chemical preservative
ADDITIVES medical devices
*it depends on the concentration of the alcohol
EXTERNAL restricted to external parts of in the preparation
D&C COLOR the body (not including the lips ● PREVENT MICROBIAL GROWTH:
ADDITIVES and other parts that are ○ 15% ALCOHOL in acid media
covered by mucous membrane ○ 18% ALCOHOL in alkaline
media.
FD&C Red No. 2 ● ALCOHOL-CONTAINING
● also known as AMARANTH PHARMACEUTICALS
(elixirs, spirits, and tinctures)
 ○ self sterilizing and do not TOPICAL POWDERS
require additional preservation. ● Should have a uniform small particle
Examples of the preservatives and their size.
concentrations commonly employed in ● Should be impalpable and free-flowing.
pharmaceutical preparations are: ● Should easily adhere to the skin.
● Passed through a No. 100 mesh sieve.
PRESERVATIVE CONCENTRATION
○ To minimize skin irritation
● Highly sorptive powders should not be
*BENZOIC ACID 0.1% - 0.2% applied to oozing wounds (wet) → hard
crust may form.
*SODIUM BENZOATE 0.1% - 0.2% ○ Hydrophobic, water repellent
powder instead.
● Usually consist of :
*ALCOHOL 15% - 20% ○ Base/Vehicle - talc or
cornstarch
PHENYLMERCURIC 0.002% - 0.01%
NITRATE & ACETATE
○ Adherent - stearates (calcium,
magnesium, or zinc)
PHENOL 0.1% - 0.5% ○ Active Ingredient
○ Aromatic Material
CRESOL 0.1% - 0.5% ● The powder should provide a large
surface area, flow easily, and spread
CHLOROBUTANOL 0.5% uniformly.
BENZALKONIUM 0.002% - 0.01% INSUFFLATED POWDERS
CHLORIDE
● Finely divided powders that are
*COMBINATIONS OF 0.1% - 0.2% intended to be applied in a body cavity
METHYL & (ears, nose, vagina, tooth socket or
PROPYLPARABEN throat)
● Insufflator or “puffer”
SOLID DOSAGE FORMS

POWDERS
● Physical form of a material - a dry
substance composed of finely divided
particles
● Type of pharmaceutical preparation
- a medicated powder
intendedforinternal (i.e. oral powder) ● POLYOX
orexternal (i.e. topical powder) use. ○ Moisture-activated adherent
● As a dosage form - intimate mixture ○ Forms a viscous,
of dry, finely divided drugs or mucoadhesive gel when in
chemicals that may be intended for contact with moisture.
internal or external use. ■ Provide a depot for
long term drug
GRANULES delivery.
● Prepared agglomerates of powdered
materials, maybe used for:
○ Medicinal value of the content
○ Pharmaceutical purpose in
making tablets
 ● MINERAL OIL (for water soluble
powders) AND GLYCERIN (for oil
soluble)

BENDING POWDERS
1. SPATULATION
PARTICLE SIZE ● Blending small amounts of powders by
● VERY COARSE (NO. 8): All particles movement of a spatula through them
pass through a No. 8 sieve and not on a sheet of paper or an ointment tile.
more than 20% pass through a No. 60 ● Not suitable for large quantities of
sieve. powders or for powders containing
● COARSE (NO. 20): All particles pass potent substances
through a No. 20 sieve and not more ● Suited to mixing solid substances that
than 40% pass through a No. 60 sieve. form eutectic mixtures (or liquefy)
● MODERATELY COARSE (NO. 40): All *Eutectic mixtures - lowering of melting point
particles pass through a No. 40 sieve
and not more than 40% pass through a 2. SIFTING
No. 80 sieve. ● mixed by passing them through sifters
● FINE (NO. 60): All particles pass like those used in the kitchen to sift
through a No. 60 sieve and not more flour.
than 40% pass through a No. 100 ● Sifting results in a LIGHT, FLUFFY
sieve. PRODUCT.
● VERY FINE (NO. 80): All particles ● This process is NOT acceptable for the
pass through a No. 80 sieve. There is incorporation of potent drugs into a
no limit to greater fineness. diluent powder.
*Crude drugs - no ‘very fine’ particle size *not widely used in pharmaceutical industry,
mostly used in food industry
COMMINUTION OF DRUGS
1. TRITURATION 3. TUMBLING
● COMMINUTION ● Mixing powders in a rotating chamber.
● Grinding a drug in a mortar to reduce • Special small-scale and large- scale
its particle size. motorized powder blenders mix
● Finer grinding action is accomplished powders by tumbling them
by using a mortar with a rough ● Mixing by this process is THOROUGH
surface (as a porcelain mortar) than BUT TIME CONSUMING.
one with a smooth surface (as a glass ● Such blenders are widely employed in
mortar). industry, as are mixers that use
motorized blades to blend powders in
2. LEVIGATION a large vessel.
● Commonly used in small-scale
preparation of ointments and PROBLEMS: MIXING POWDERS
suspensions to reduce the particle size SEGREGATION
and grittiness of the added powders. ● an undesirable separation of the
● A mortar and pestle or an ointment tile different components of the blend.
may be used. 1. SIFTING OR PERCOLATION
● A paste is formed by combining the 2. AIR ENTRAPMENT
powder and a small amount of liquid (FLUIDIZATION)
(the levigating agent) in which the 3. PARTICLE ENTRAPMENT
powder is insoluble. (DUSTING).
● FIGURE 8 TRACK
 1. 3SIFTING PARCHMENT resistant paper.
● Fine particles tend to sift or
percolate through coarse WHITE BOND An opaque paper with no
particles a moisture resistant properties
● End up at the bottom of the
GLASSINE A glazed, transparent
container and actually “lift” the moisture resistant paper
larger particles to the surface.
2. FLUIDIZATION WAXED PAPER Transparent waterproof paper.
● Fine, aerated powders with
*opaque = provides protection for photosensitive
differences in particle size or substances
density may result in a
striation pattern (layering) TYPE OF PAPER BASED ON THE NATURE
● May occur during powder OF POWDER:
transfer
NATURE OF POWDER TYPE OF PAPER

3. DUSTING HYGROSCOPIC & WAXED PAPER

● Occurs when the finer, lighter DELIQUISC
particles remain suspended in
air longer WITH VOLATILE WAXED OR GLASSINE
COMPONENTS (ex.
● Do not settle as quickly as the
With Essential oils)
larger or denser particles.
LIMITED BARRIER GLASSINE OR
BULK AND DIVIDED POWDERS NEED VEGETABLE
1. BULK POWDERS PARCHMENT
● Examples:
WITHOUT VOLATILE SIMPLE BOND
○ antacids, douche powders, SUBSTANCE OR NOT
medicated powders for external AFFECTED BY
application, Brewer’s yeast and MOISTURE
nutritional supplements.
○ Measuring scoop and spoon GRANULES
● Limited to NON-POTENT ● Usually 4 to 12 mesh sieve size
SUBSTANCES ranges.
● Patients → educated about: ● Prepared by Wet and Dry method
○ Handling ● Characteristics:
○ Storage ○ FLOW WELL compared to
○ Measurement powders
○ Preparation ○ Surface area is less than that of
2. DIVIDED POWDERS a comparable volume of
● Small paper (Latin Chartula; abbrev. granules
Chart.; powder paper) ■ MORE STABLE to the
● Preparation: effects of atmospheric
GEOMETRIC DILUTION → POTENT humidity
SUBSTANCE ○ LESS LIKELY TO CAKE or
– Block and divide harden upon standing
– Weigh individually ○ EASILY WETTED by liquid
*popular intermediate products in tablets
POWDERS PAPERS
TYPE OF PAPER PROPERTIES

VEGETABLE A thin semi-opaque moisture

EFFERVESCENT GRANULATED SALTS ○ Gelatin
● Granules or coarse to very coarse ○ Sugar
powders containing a medicinal agent ○ Water
in a dry mixture. ● May be colored with various FD&C and
● usually composed of sodium D&C
bicarbonate, citric acid and tartaric ● Opaque - TITANIUM DIOXIDE
acid.
○ Citric acid alone → STICKY GELATIN (main ingredient of capsules)
MIXTURE ● Partial hydrolysis of collagen obtained
○ Tartaric acid alone → LOSE from the skin, white connective tissues
FIRMNESS AND CRUMBLES and bones of animals.
● Carbonated solution masks ● Prone to microbial contamination -
undesirable taste moist
● Granules → to decrease rate of ● Soluble in hot water
solution ● A protein → digested by proteolytic
○ Prevent violent and enzymes and absorbed.
uncontrollable effervescence
*smaller particle size = fast reaction with water GELATIN SHELL
● Contains 13% to 16% moisture
METHOD OF PREPARATION ● HIGH HUMIDITY - distorted & lose
1. DRY METHOD OR FUSION rigid shape
● Binding agent → molecule of ● LOW HUMIDITY/ EXTREME
water present in each molecule DRYNESS - brittle and crumble
of citric acid ● STORAGE: environment free from
○ C6H8O7.H20 excessive humidity or dryness
● Equipment → stainless steel ● Desiccant material
(acid resistant) ○ Small packets
● Low humidity prevent ○ Example:
absorption of moisture ■ Dried Silica Gel
2. WET METHOD ■ Clay
● Source of binding agent: water ■ Activated Charcoal
added to alcohol
HEIDELBERG CAPSULE
CAPSULES ● Approximate size of a No. 0 gelatin
● Solid dosage forms in which medicinal capsule, has been used as a
agents and/or inert substances are nonradioactive means to:
enclosed in a small shell. 1. Measure gastric Ph
○ Maybe hard or soft depending 2. Gastric residence time and
on their composition. gastric emptying time of solid
○ Maybe composed of two pieces dosage forms in fasting and
(body and cap) or single piece. non-fasting human subjects.
○ Hard-shell capsule - two piece
○ Soft-shell capsule - one piece MANUFACTURE OF HARD GELATIN
CAPSULES
HARD GELATIN CAPSULE ● 2 Sections: BODY and the CAP
● Used in most commercial medicated *Usually the body is longer in length
capsules compared to the cap
● Employed in clinical trials ● Shells produced by mechanical dipping
● Extemporaneous compounding of of pins or pegs of the desired shape
prescriptions and diameter into a temperature
● Made of:
 controlled reservoir of melted gelatin
mixture.
● PEGS: MANGANESE BRONZE

DISTINCTIVE LOOKING CAPSULES

● PULVULES (Eli Lily)
○ Body-tapered
○ Cap-rounded
● SPANSULES (Smithkline Beecham)
○ Both the ends of the cap &
body is tapered
● SNAP FIT, CONI-SNAP &
CONI-SNAP SUPRO CAPSULE FORMULATION EXCIPIENT
○ Enables two halves of the
capsules shells to be positively 1. DILUENT
joined through locking ● Added to produce the proper
grooves in the shell walls. capsule fill volume
● Provide COHESION to
DISTINCTIVE LOOKING CAPSULES powders
● EXAMPLES: “SMiLE”
○ Lactose
○ Microcrystalline
cellulose
○ Starch
2. DISINTEGRANTS
● Assist BREAK UP and
distribution of the capsules
contents in the stomach.
● EXAMPLES: “CroPSSS”
○ Pregelatinized starch
○ Croscarmellose
CAPSULE SIZES ○ Sodium starch glycolate
● For human use: capsule ranging in 3. LUBRICANT OR GLIDANT
size from 000 (the largest) to 5 ● Industrial scale: high speed
(smallest) automated equipment
● Larger capsules → available for ● ENHANCES FLOW
veterinary use PROPERTIES
● SIZE SELECTION: ● EXAMPLES:
○ Determined by amount of fill to ○ Fumed silicon dioxide
be encapsulated ○ Calcium stearate
○ Density and compressibility ○ Stearic acid
○ Approximation ○ Talc
○ Trial and error ❖ MAGNESIUM STEARATE (most
popular)
CAPSULE SIZES ➢ Water-insoluble
000 (BIGGEST),00,0,1,2,3,4,5 (SMALLEST) ➢ PROBLEM:
WATERPROOFING - delay
dissolution and absorption
➢ REMEDY:
■ Surface active agent
 ■ SODIUM LAURYL ○ Minimize wear of punches and
SULFATE: used to dies
facilitate wetting by the ○ Prevent fill material from
GIT fluid sticking to punches and dies
○ Produce tablets with sheen
TABLET AND MODIFIED RELEASE ● Miscellaneous adjuncts
TABLETS ○ Colorants and flavorants
● Solid dosage forms usually
prepared with the aid of suitable MULTIPLE COMPRESSED TABLETS
pharmaceutical excipients. ● Prepared by subjecting the fill material
● Vary in size, shape, weight, hardness, to more than a single compression.
thickness, disintegration and ● Result:
dissolution characteristics depending A. Tablet within a tablet
on their use and method of ● Inner tablet - CORE
manufacture. ● Outer portion - SHELL
● Most tablets used in oral B. Multiple layer tablet
administrations ● Each layer may contain a
● Other routes of administration: different medicinal agent,
○ Sublingually separated for reasons of:
○ Buccally ○ Chemical and physical
○ Vaginally incompatibility
○ Staged drug release
SCORED OR GROOVED TABLETS ○ Unique appearance of
● Easily broken into two or more parts the layered tablet
● Enables the patient to swallow smaller ● EXAMPLE: Neozep Tablet
portions
● Allows the tablet to be taken in SUGAR COATED TABLETS
reduced or divided dosage. ● Coated with a colored or an
● IF NOT SCORED: uncoloured sugar layer.
○ Not intended to be broken or ● Coating is water soluble and quickly
cut by the patient → may have dissolves after swallowing.
special coating and/or drug ● Sugarcoat:
release features. ○ Protects the enclosed drug
from the environment
COMPRESSED TABLETS ○ Provides barrier to
PHARMACEUTICAL ADJUNCTS: objectionable taste and odor
● Diluents or fillers ○ Enhances the appearance and
○ To prepare tablets of the permits imprinting of identifying
desired size manufacturer’s information.
● Binders or adhesive ○ Add 50% to the weight and
○ Promote adhesion of the bulk of the uncoated tablet.
particles of the formulation
● Disintegrants or disintegrating FILM-COATED TABLETS
agents ● Compressed tablets coated with a thin
○ Promote break-up of the tablet layer of polymer capable of forming a
after administration to smaller SKINLIKE film.
particles ● Designed to rupture and expose the
● Antiadherents, glidants, lubricants, core tablet at the desired location in
or lubricating agents. the GIT fluid. Usually colored
○ Enhance the flow of the ● ADVANTAGES: Over sugar-coated
material into tablet dies table
 ○ More durable
○ Less bulky
○ Less time-consuming to
prepare

GELATIN-COATED TABLETS
● A capsule shaped compressed tablet
that allows the coated product to be
about one-third smaller than a
capsule filled with an equivalent
amount of powder.
● Gelatin Coating CHEWABLE TABLETS
○ Facilitates swallowing and more ● Have a smooth, rapid disintegration
tamper evident than unsealed when chewed or allowed to dissolve in
capsules. the mouth.
● GELCAPS - innovator product ● Have a creamy base → flavored and
colored MANNITOL
ENTERIC-COATED TABLETS ● Sugar free tablet: Xylitol
● Have DELAYED RELEASE feature. ● Useful for administration of large
● Designed to pass UNCHANGED tablets to children and adults who have
through the stomach to the intestines difficulty swallowing (dysphagia) solid
(target site), where tablets disintegrate dosage forms.
and allow drug dissolution and
absorption and effect. EFFERVESCENT TABLETS
● Employed when: ● Prepared by compressing granular
○ Drug substance destroyed by effervescent salts that release gas
gastric acid when in contact with water.
○ Irritating to the gastric mucosa ● Contain medicinal substances that
○ Enhance drug absorption dissolve rapidly when added with
water.
BUCCAL AND SUBLINGUAL TABLETS ○ BUBBLE ACTION - can assist
● Flat, oval tablets intended to be in breaking up the tablets and
dissolved in the buccal pouch or enhancing the dissolution of the
beneath the tongue for absorption active ingredient.
through the oral mucosa. ○ e.g. Berocca tab, Fluimucil
● Employed when: tablet
○ Drugs are destroyed by the
gastric juice MOLDED TABLETS
○ Poorly absorbed in the GIT ● Example: TABLET TRITURATES
● BUCCAL TABLETS - designed to ● Prepared by molding
erode slowly ● Very soft and soluble and are designed
● Sublingual tablet - dissolves promptly for rapid dissolution.
and provides rapid drug effects.
● LOZENGES OR TROCHES - TABLET TRITURATES
disc-shaped solid dosage forms ● Small, usually cylindrical, molded or
containing medicinal agents and compressed tablets containing small
generally a flavoring substance in a amounts of usually potent drugs.
hard candy or sugar base. ● Diluent: Combination of SUCROSE
○ Intended to be slowly dissolved AND LACTOSE
in the oral cavity.
 ● Example: NITROGLYCERIN ● Liquefy on the tongue and allows the
TABLETS patient to swallow the liquid
● Compounding: triturates are inserted ● Designed for children and elderly
into capsules or dissolved in liquid to ○ Difficulty in swallowing tablets
provide accurate amounts of potent ● ZYDIS DELIVERY SYSTEM - First
drugs. entry into the RDT field
○ Fastest disintegrating system
HYPODERMIC TABLETS on the market
● NO LONGER AVAILABLE - due to ○ Dissolves in the tongue in a
prefabricated injection products in few seconds
disposable syringes. ● PREPARATION:
● Used by physicians in: ○ Foaming a mixture of gelatin,
EXTEMPORANEOUS PREPARATION sugar or sugars, drug
OF PARENTERAL SOLUTIONS. ○ Foam poured into mold
● Dissolved in a suitable vehicle, sterility ■ Mold - serves as the
attained, and the injection performed. unit dose dispensing
● Convenient → easily carried in package
physician’s medicine bag and ○ Foam-lyophilized
injections prepared to meet the needs ○ Package
of the individual patients.
● Disadvantage: DIFFICULTY IN
ACHIEVING STERILITY

DISPENSING TABLETS
● No longer in use.
● Compounding Tablets
○ Used by pharmacists to
compound prescriptions
● Contained LARGE amounts of highly
VAGINAL TABLETS
potent drug substances → so
● Also called: VAGINAL INSERTS
pharmacists could rapidly obtain pre
● Uncoated, bullet shaped or ovoid tablet
measured amounts for compounding
● Inserted to the vagina for local effects
multiple dosage units.
● Contains antibacterial or antifungals
● CAUTION: DO NOT DISPENSED TO
Treatment of:
THE PATIENT
○ Vaginitis
■ Haemphilus vaginalis
IMMEDIATE RELEASE TABLETS
○ Vulvovaginitis candidiasis
● Designed to disintegrate and release
■ Candida albicans
their medication with no special
● PREPARATION:
rate-controlling features.
○ Compression and shaped to fit
● No special coatings
snugly on plastic inserter
device that accompany the
RAPIDLY DISINTEGRATING OR
product
DISSOLVING TABLETS
● Instant release tablets or rapidly
dissolving tablets (RDT’s)
● Characterized by dissolving or
disintegrating in the mouth
within 1 minute or some within 10
seconds.
Ex: Clarinex Reditabs (Loratadine)
 OTHER SOLID DOSAGE FORMS FOR ● Administered orally or parenterally
ORAL ADMINISTRATION ● Used to provide:
○ Physical separation for
LOZENGES (TROCHES) chemically or physically
● Solid oral dosage forms that are incompatible materials
designed to dissolve or disintegrate ○ Extended release
slowly in the mouth ○ Delayed release
● Flavored and sweetened base ● Size: 710 um to .36 mm
● Used for both local and systemic effect
● Examples: BOLUS TABLETS
○ Antiseptic, analgesics, ● Are large, usually elongated tablets
decongestants, anti-tussives, intended for administration to large
and antibiotics animals.
● Can be made by compression or ● Conventional tableting processes can
molding be used to manufacture
● Molded Lozenges: cough drops or ○ Higher compression forces may
PASTILLES (gelatin based) be necessary

LOLLIPOPS PILLS
● FENTANYL ACTIQ (Cephalon) ● Are small, round solid dosage forms
○ Raspberry lollipop that is containing a medicinal agent intended
sugar-based lozenge on a stick to be administered orally.
and contains fentanyl citrate. ● Prepared by:
○ First product specifically ○ Wet massing and molding
designed to aid in controlling technique
breakthrough pain in cancer ● Have been replaced by tablets and
patients with malignancies who capsules.
are already taking and are *Connotes a medicine that is taken on a daily
tolerant to opioids. basis
○ The lollipop provides almost *no longer use as a dosage form
immediate relief as the drug
starts being absorbed in the
mouth and starts to work within SOLID ORAL MODIFIED RELEASE
minutes. DOSAGE FORMS AND DRUG DELIVERY
SYSTEMS

TERMINOLOGIES
● MODIFIED RELEASE
○ Use to describe dosage forms
having drug release features
based on time, course,
and/or location that are
designed to accomplish
therapeutic objectives not
PELLETS offered by conventional or
● Composed of small, solid particles of immediate release.
uniform shape sometimes called ● EXTENDED RELEASE
BEADS. ○ One that allows a reduction in
● Are nearly spherical, but not a dosing frequency from that
requirement. necessitated by a conventional
dosage form, such as a solution
 or an immediate release prepared to have varying drug-release
dosage form. characteristics.
● DELAYED RELEASE ○ May be placed in gelatin
○ Designed to release the drug at capsule shells to provide the
a time other than promptly desired pattern of drug release.
after administration. ○ Each capsule may contain 8 to
○ Delay may be: 10 mini tablets, some uncoated
■ Time based for immediate release and
■ Based on the influence others coated for extended
of environmental drug release.
conditions (GIT pH)
● REPEAT ACTION
○ Usually contain two single
doses of medication:
■ One for immediate
release and the second
for delayed release
■ Example: Two layer
tablets
*Purpose is to minimize dosing frequency

● TARGETED RELEASE
○ Drug release directed toward
isolating or concentrating a
drug in a body region, tissue,
or site for absorption or for
drug action.
MICROENCAPSULATION DRUG
Example: Implants
Microencapsulation:
● A process by which solids, liquids, or
EXTENDED RELEASE TECHNOLOGY FOR
even gasses may be enclosed in
ORAL DOSAGE FORMS
microscopic particles by formation of
thin coatings of wall material around
COATED BEADS, GRANULES AND
the substance.
MICROSPHERES
● Wall forming material:
● Prepared using:
○ Gelatin
○ Conventional pan coating
○ Synthetic polymers
○ Air suspension coating
■ Polyvinyl alcohol,
● Beads made of:
ethylcellulose, polyvinyl
○ Sugar and starch or
chloride
microcrystalline cellulose
● Different rates of drug release may be
spheres
obtained by changing the ratio of core
○ Nonpareil seeds: 425 to 850
to wall, the polymer used for coating,
mm
and the method of microencapsulation.
○ Microcrystalline cellulose
spheres: 170 to 600 mm
EMBEDDING DRUG IN INERT PLASTIC
■ Considered more
MATRIX
durable during
● Drug is granulated with an inert plastic
production
material such as:
MULTI TABLET SYSTEM
○ Polyethylene
● Small spheroid compressed tablets 3
○ Polyvinyl acetate
to 4 mm in diameter and may be
 ○ Polymethacrylate

● Granulation is compressed into tablets

● The drug is slowly released from the
inert plastic matrix by diffusion
● Immediate release portion of the drug REPEAT ACTION TABLETS
may be compressed onto the surface ● Prepared so that an initial dose of drug
of the tablet. is released immediately and a second
● Inert tablet matrix, expended of drug, is dose follows later.
excreted with the feces. ● Example:
○ Repetabs (Schering)
COMPLEX FORMATION ● Best suited for treatment of chronic
● Drug substances when combined with conditions requiring repeated dosing.
certain other chemical agents- form ● Drugs should have low dosage and
complexes that may be only slowly fairly rapid rates of absorption and
soluble in body fluids excretion
○ Depending on the pH of the
environment. SEMISOLID DOSAGE FORMS
○ Slow dissolution rate provides (OINTMENTS, CREAMS, AND PASTES)
the ER of the drug
● Release of drug depends on the pH OINTMENTS
and electrolyte concentration in the ● Semisolid preparations intended for
GIT external applications to the skin or
● Release is greater in the acidity of the mucous membranes.
stomach than in the less acidic ● May be medicated or not.
environment ● Un-medicated
OSMOTIC PUMP ○ Used for the physical effects
● OROS system - pioneer oral osmotic they provide as:
pump drug delivery developed by Alza ■ Protectants
○ Composed of a core tablet ■ Emollients
surrounded by a semi- ■ Lubricants
permeable membrane coating
having a 0.4 mm diameter hole OINTMENT BASES
produced by laser beam. 1. Oleaginous
○ Core tablet has two layers: 2. Absorption
■ Active layer (containing 3. Water-Removable
the drug) 4. Water-Soluble
■ Push layer (containing a
polymeric osmotic
agent) 1. OLEAGINOUS BASES
● The system operates on the principle ● Also termed: HYDROCARBON
of osmotic pressure. BASES
● On application to the skin:
○ Emollient effect
○ Protect against the
escape of moisture
○ Are effective as
occlusive dressings
 ○ Can remain on the skin d. WHITE OINTMENT
for long periods without ● Differs from yellow ointment by
drying out substitution white wax and white
○ Because of their petrolatum in the formula.
immiscibility with water,
they are difficult to wash 2. ABSORPTION BASES
off. ● TWO TYPES:
● Water and aqueous ○ Those that permit the
preparations: incorporation of aqueous
○ May be incorporated solutions → W/O emulsion
and with some difficulty. ■ Hydrophilic Petrolatum
USP
● Powdered Substance: ■ Anhydrous Lanolin
○ Liquid petrolatum / ■ Aquaphor
Mineral oil - Levigating ○ Those that are W/O emulsion
agent that permit the incorporation of
additional quantities of aqueous
solutions.
■ Cold cream
a. PETROLATUM USP ● Used as emollients
● Purified mixture of semisolid ○ They DO NOT provide the
hydrocarbons obtained from degree of occlusion afforded by
petroleum. oleaginous bases.
● Also known as: ● Useful pharmaceutical adjuncts to
○ Yellow Petrolatum incorporate small volumes of aqueous
○ Petroleum Jelly solutions into hydrocarbons.
● An unctuous mass, varying in color
from yellow to light amber. a. HYDROPHILIC PETROLATUM USP
● Melts at 38 to 60 OC May be used ● Formulation:
alone or in combination ○ Cholesterol
○ Stearyl Alcohol
b. WHITE PETROLATUM ○ White wax
● Purified mixture of semisolid ○ White petrolatum
hydrocarbons from petroleum that has ● Preparation: Fusion
been wholly or nearly decolorized. ● Commercial Product: Aquaphor
● Lighter Color: ● A variation of hydrophilic
○ More esthetically pleasing than petrolatum.
petrolatum ● Has the capacity to absorb up
● Commercial Product: to THREE TIMES its weight in
water and useful to help
● White Vaseline (Chesebrough-Ponds) incorporate water-soluble drug
into an oleaginous base.
c. YELLOW OINTMENT USP
● AKA: SIMPLE OINTMENT b. LANOLIN USP
● Slightly greater viscosity than plain ● AKA: ANHYDROUS LANOLIN
petrolatum ● Obtained from the wool of sheep (Ovis
● FORMULATION aries)
○ Yellow wax - Stiffening agent ● A purified wax like substance that has
○ Petrolatum - Base been cleaned, deodorized and
decolorized.
 ● Additional water may be incorporated ○ Above 1000
by MIXING. ○ wax like white materials
● MODIFIED LANOLIN ● Formulation:
○ Lanolin processed to reduce ○ PEG 3350
the contents of free lanolin ○ PEG 400
alcohols and any detergent and ● FIRMER OINTMENT
pesticide residues. ○ Equal parts of the two
ingredients
3. WATER-REMOVABLE BASES ● Incorporation of Aqueous solution
● O/W emulsion → RESEMBLING ○ Substitution of 50g PEG 3350
CREAMS with an equal amount of
STEARYL ALCOHOL→ firmer
● Easily washed from the skin → Water
washable base SELECTION OF THE APPROPRIATE BASE
● May be diluted with water or aqueous ● Dry, scaly skin
solutions ○ Ointment
● Consists of 3 PARTS: ● Weeping or oozing surfaces
1. OIL PHASE ○ Cream
2. WATER PHASE ● Intertriginous areas
3. EMULSIFIERS ○ Lotion
● Can absorb serous discharge
PREPARATION OF OINTMENTS
a. HYDROPHILIC OINTMENT USP
● Formulation: INCORPORATION
○ Methylparaben ● Components are mixed until a uniform
■ Preservative preparation is attained.
○ Propylparaben ● Extemporaneous compounding:
■ Preservative ○ Mortar and pestle
○ Sodium lauryl sulphate ○ Ointment slab and spatula
■ Emulsifying agent ○ Non-absorbent parchment
○ Propylene glycol paper
○ Stearyl alcohol ■ Do not allow too long
○ White Petrolatum contact of the ointment
○ Purified water with the parchment as it
● Preparation: Fusion may soften or tear.
● Ointment Mill
4. WATER-SOLUBLE BASES ● Electronic Mortar and Pestle
● DO NOT contain oleaginous ○ UNGUATOR
components ○ The ingredients in a plastic
● Referred to as: GREASELESS ointment jar with a special lid
● Soften greatly with the addition of that allows for a mixing blade to
water. be used to mix the ingredients
● Mostly used for incorporation of solid in the dispensing container.
substances.
FUSION
a. POLYETHYLENE GLYCOL ● Components of an ointment are
● A polymer of ethylene oxide and water combined by being melted together
○ Below 600 and cooled with constant stirring until
■ clear, colorless liquids congealed.
○ 600-1000 ● Heat-Labile & Volatile Substance
■ Semisolids
 ○ ADDED LAST → when the ■ Rectally
temperature of the mixture is ■ Vaginally
low enough not to cause ● Preferred to ointments because
decomposition or volatilization. they are easier to spread and
● On small scale: remove
○ Porcelain Dish
○ Glass Beaker GELS
● On large scale: ● aqueous liquid vehicle rendered jelly
○ large steam jacketed kettles like by the addition of a gelling agent.
● Ointment bases prepared by Fusion: ● Gelling Agents:
○ Beeswax ● Synthetic macromolecules
○ Paraffin ○ Carbomers
○ Stearyl alcohol ○ High molecular weight
○ High-molecular-weight PEGs water-soluble polymers
of acrylic acid
MICROBIAL CONTENT cross-linked with allyl
Ophthalmic - STERILE ethers of sucrose and/or
Topical: pentaerythritol
● Preservatives: ○ Concentration: 0.5% to
○ Parabens 2.0%
○ Phenols ○ Example: Carbomer 934
○ Benzoic acid ● Cellulose derivatives
○ Sorbic acid ○ CMC
○ Quaternary ammonium salts ○ HPMC ( commonly used
● Must meet the requirements for in sanitizing gels)
absence of: ● Natural Gums
○ Staphylococcus aureus ○ Tragacanth
○ Pseudomonas aeruginosa ● May thicken on standing forming
■ Example: THIXOTROPE (reversible sol-gel
Betamethasone valerate formation)
○ Must be shaken before use to
CREAMS liquefy the gel and enable
● Semisolid preparations containing one pouring.
or more medicinal agents dissolved or
dispersed in either a W/O emulsion or Two Types of Gels
in an oil-water emulsion or in another ● SINGLE-PHASE GELS
type of water-washable base. ○ Macromolecules are uniformly
● VANISHING CREAMS distributed throughout a liquid
○ O/W with no apparent boundaries
○ Contains large percentages of between the dispersed
water and STEARIC ACID or molecules.
other oleaginous components. *homogeneous in appearance compared to
○ After application: two-phase system
■ The water evaporates - ● TWO-PHASE SYSTEM
leaving behind a thin ○ Consisting of floccules of
residue of the stearic small distinct particles
acid or oleaginous ○ Often referred as: Magma
components. ○ Example: Milk of Magnesia
● Primary Application: ■ AKA: Magnesia Magma
○ Topical skin products
○ Products used:
 ■ Consists of a gelatinous ○ Example:
precipitate of ■ Salicylic acid Plaster
magnesium hydroxide. ● removal of corns
● Keratolytic
MISCELLANEOUS SEMISOLID ● Concentration:
PREPARATIONS 10% to 40%

PASTES GLYCEROGELATINS
● Semisolid preparations intended for ● Plastic masses containing gelatin
application to the skin. (15%), glycerine (40%), water (35%),
● Contain a larger proportion of solid and an added medicinal substance
material (25%) (10%).
● Stiffer ● Applied to the skin for LONG TERM
○ remain in place after application ● Melted before application, cooled to
○ effectively employed to absorb slightly above body temperature, and
serous secretions applied to the affected area with a fine
○ not suited for application to brush → harden (covered with
hairy parts of the body bandage).
● Preparation: the same with ointment ● Allowed to remain in place for weeks.
○ Levigating agent is to be ● Example:
used: ○ Zinc gelatin
■ a portion of the base is ■ USE: Treatment of
used rather than a varicose ulcers.
liquid. ■ AKA: Zinc Gelatin Boot
● Ability to form a
ZINC OXIDE PASTE pressure
● LASSAR’S PLAIN ZINC PASTE bandage
● Prepared by mixing 25% each of zinc
oxide and starch with petrolatum. TRANSDERMAL DRUG DELIVERY SYSTEM
● Firm and better able to protect the skin
and absorb secretions. TRANSDERMAL DRUG DELIVERY SYSTEM
● Facilitate the passage of therapeutic
PLASTERS quantities of drug substances through
● Solid or semisolid adhesive masses the skin and into the GENERAL
spread on a backing of paper,fabric, CIRCULATION for their systemic
moleskin, or plastic. effects
● Adhesive material ● STOUGHTON
○ rubber base or a synthetic resin ○ First conceived of the
● Applied to the skin to provide percutaneous absorption of
prolonged contact at the site. drug substances
● TRANSDERM SCOP
● Un-medicated Plasters ○ Scopolamine
○ Provide protection or ○ First transdermal system
mechanical support at the site ■ approved by the FDA in
of application 1979
○ Ex. Band Aid ○ USE: for prevention of nausea
● Medicated Plasters and vomiting associated with
○ provide effects at the site of travel, particularly at sea.
application
○ may be cut to size to conform
to the surface to be covered
 FACTORS AFFECTING PERCUTANEOUS ○ Increase hydration of the
ABSORPTION stratum corneum
○ Solvent action or
1. DRUG CONCENTRATION Denaturation
○ INCREASE Concentration of ■ change in the structure
the drug (TDDS) = INCREASE of the lipids and
amount absorbed lipoproteins in the
2. AREA OF APPLICATION intercellular channels
○ LARGER TDDS = MORE Drug ● SELECTION
absorbed ● Efficacy in enhancing skin
3. Drugs should have a GREATER permeation
PHYSICOCHEMICAL ATTRACTION ● Dermal toxicity (Low)
to the skin than to the vehicle. ● Physicochemical and
○ SOLUBILITY OF DRUG Biologic compatibility
● DRUG - Both lipid and ● Examples:
water soluble ○ Acetone
● Water solubility ○ Azone
○ concentration at ○ dimethyl acetamide
absorption site ○ dimethyl formamide
● Partition coefficient ○ dimethyl sulfoxide
○ Influences rate ○ Ethanol
of transport ○ Oleic acid
across the ○ PEG
absorption site. ○ propylene glycol
4. MOLECULAR WEIGHT ○ Sodium lauryl sulphate
○ LOW MW → Better absorption
○ Ideal MW PHYSICAL METHODS
■ 400 or less IONTOPHORESIS
5. HYDRATION ● Delivery of a charged chemical
○ TDDS - occlusive barrier compound across the skin membrane
○ Sweat cannot pass → Increase using an electrical field.
Skin Hydration → Increase ● Being studied:
Percutaneous absorption ○ Lidocaine
6. APPLICATION SITE ○ Dexamethasone
○ Thin horny layer → Increase ○ Amino acids
absorption ○ Peptides
7. APPLICATION TIME ○ Insulin
○ Longer Application Time → ○ Verapamil
GREATER Drug Absorption ○ Propranolol
● NuPathe’s SUMATRIPTAN (Zecuity)
Ionotophoretic Patch
PERCUTANEOUS ABSORPTION ○ Treatment of Migraine in Adults
ENHANCERS
SONOPHORESIS
CHEMICAL ENHANCERS ● High-frequency Ultrasound
● “Increases skin permeability by ○ can influence the integrity of
reversibly damaging or altering the the stratum corneum and thus
physicochemical nature of the affect its penetrability
stratum corneum to reduce ○ The drug is in gel form
diffusional resistance” ● Being studied as a means to enhance
transdermal drug delivery.
 ● Agent examined: ○ Rate controlling membrane
○ Hydrocortisone ○ Adhesive and protecting
○ Lidocaine layers
○ Salicylic acid ● A small quantity of drug is frequently
placed in an adhesive layer to initiate
DESIGN FEATURES of TRANSDERMAL prompt drug absorption and
DRUG DELIVERY SYSTEM pharmacotherapeutic effects on the
1. Monolithic System skin placement.
2. Membrane Controlled System
MONOLITHIC SYSTEM ● Example:
● Incorporate a drug matrix layer ○ Transderm-Nitro (Summit)
between the backing and the frontal ○ Transder-Scop (Baxter)
layers.
● Drug-matrix layer
○ composed of a polymeric
material in which the drug is
dispersed
○ The polymer is the vehicle of
the drug and responsible for
rate of release
● Polymer matrix
○ controls the rate of
percutaneous absorption LAYERS
○ Two types: 1. Occlusive backing membrane
1. With excess of drug ● to protect the system from
○ A drug reservoir is present to environmental entry
ensure continued saturation at ● prevent loss of drug from the
the stratum corneum system or moisture from the skin
○ Rate of drug decline is less ● MUST BE occlusive to retain skin
2. Without excess of drug moisture and hydrate the site of
○ Drug is available to maintain application → enabling skin
the saturation of the stratum penetration.
corneum only as long as the ● Material Used: Transparent or
level of the drug exceeds the pigmented films of polyethylene,
solubility limit of the stratum polypropylene, and polyolefin.
corneum. 2. Drug reservoir or matrix system
- Store and release the drug at the skin
site
3. Release liner
- Removed before application and
enables drug release
4. Adhesive layer
● Maintain contact with skin after
application
● Some TDDSs
○ contains the drug
MEMBRANE CONTROLLED ● POLYBUTYL ACRYLATE
TRANSDERMAL SYSTEM ○ Commonly used
● Designed to contain: adhesive in TDDSs
○ Drug reservoir or pouch ● MUST BE:
■ Liquid or gel form ○ Pressure sensitive
 ○ To provide the ability to anesthetics and analgesic in
adhere to the skin with surgery
minimal pressure and ● DESCRIPTION:
remain in place for the ○ Circular flat patch 0.2 mm thick
period intended of wear. and 2.5 cm 2 in area.
○ Non-irritating ○ Four-layer system
○ Allow easy peel-off after ○ Contains 1.5 mg Scopolamine
use ○ Design Delivery
○ Permit unimpeded drug ○ Deliver 1 mg of scopolamine at
flux to the skin a constant rate over 3-day
○ Compatible with other lifetime of the system
system components ○ Initial priming dose → 200 ug
(adhesive layer)
ADHESIVE LAYER
TWO TYPES: TRANSDERMAL NITROGLYCERIN
1. PERIPHERAL ● USE:
● contains adhesive around the ○ Prophylactic treatment of
outer edge of the TDDs angina
● Usually in a wide strip ● DELIVERY SYSTEM:
surrounding the active drug ○ Maintains drug delivery for 24
portion. hours after application.
● Ex. Band Aid ● TOLERANCE:
2. FACE ADHESIVE ○ Major factor limiting the
● covers the entire face of the effectiveness of these systems
TDDSs are packaged in when used continuously for
individually sealed packets to more than 12 hours per day
preserve and protect them until ○ REMEDY:
use. ○ Adjust Dosing schedule
● Ex. Salon pas ■ “Patch on”- 12-14 hrs
TESTED FOR: ■ “Patch off”- 10-12 hrs
● Skin compatibility
● Test for Irritation TRANSDERMAL CLONIDINE
● Sensitivity Test ● First transdermal system for
● Cytotoxicity hypertension (Catapres TTS -
Clonidine Transdermal Therapeutic
DISADVANTAGE System)
1. Only POTENT DRUGS are suitable ● Four layer patch
candidates. ● Provides controlled release of
2. Patients develop CONTACT clonidine for 7days.
DERMATITIS → DISCONTINUATION ● Clonidine:
○ Lipid solubility
EXAMPLES OF TRANSDERMAL PATCH ○ High volume of distribution
AVAILABLE IN THE MARKET ○ Therapeutic effectiveness in
low plasma concentration.
TRANSDERMAL SCOPOLAMINE
● USE: TRANSDERMAL NICOTINE
○ Prevent travel-related motion ● USE:
sickness ○ Adjunct in SMOKING
○ Nausea and vomiting that result CESSATION
from the use of certain ○ Provide sustained blood levels
of nicotine as nicotine
 replacement therapy to help the ○
to be placed under the body -
patient establish and sustain rectum
remission from smoking. Commonly used:
● DOSE: 1. Rectally
○ 7 to 21 mg for daily application 2. Vaginally
ranging from 6 to12 weeks. 3. Urethrally
○ Available in 21 mg 14 mg, 7mg
● HOW TO USE: Type Weight Description/Shape
○ Applied to the arm or upper
front torso with patients RECTAL Adult - 2g ● 32 mm
advised not to smoke when (Cocoa butter) (1.5in.) long
wearing the system. ● Cylindrical
Infant and ● Have one or
○ Replaced daily with sites Children both ends
alternated. - half the weight tapered
○ Gradual reduction and size of the ● Bullet
TRANSDERMAL ESTRADIOL adult ● Torpedo
● Little finger
● USE: ● Pencil-like-
○ Treatment of moderate to infant and
severe vasomotor symptoms children
associated with menopause,
female hypogonadism, female VAGINAL 5g (Cocoa butter) ● Globular
(Pessaries) ● Oviform
castration, primary ovarian ● Cone-shape
failure and atrophic conditions. d
○ Hormone replacement therapy
● THERAPY:
○ Usually administered on a URETHRAL Male - 4g (Cocoa ● Slender
(Bougies) butter) ● Pencil-shape
cycling schedule (3 weeks of Female - 2g d
therapy followed by 1 week (Cocoa butter) ● Male - 3 to 6
without) mm
● HOW TO USE: (diameter)
and 140 mm
○ Applied to a clean, dry area of
(length)
the skin on the trunk of the ● Female - half
body,either the abdomen or the length
upper quadrant of the buttocks. and weight of
○ SHOULD NOT be applied to the male
● 70 mm
the waistline because tight (length)
clothing may damage or
dislodge it.
LOCAL ACTION
SUPPOSITORIES AND INSERTS ● Glycerin Suppository
○ Laxative
SUPPOSITORIES ○ Promote laxation by local
● Solid dosage forms intended for irritation of the mucous
insertion into body orifices where they membrane by dehydrating
melt or dissolve and exert local or effect on the glycerin.
systemic effects. ● Vaginal Suppositories and Inserts
● Latin: ○ Contraceptives
○ Supponere - “to place under” ■ Nonoxynol-9
○ Sub - “under” ○ Antiseptics in feminine hygiene
○ Ponere - “to place” ○ Combat invading pathogens
■ Trichomonacides
 ● (Vaginitis) ● An effective route in the treatment of
● Urethral Suppository patients with vomiting.
○ Antibacterial
○ Local Anesthetic
■ Preparative for urethral SOME FACTORS OF DRUG ABSORPTION
examination FROM RECTAL SUPPOSITORIES

SYSTEMIC ACTION PHYSIOLOGIC FACTORS

● Mucous membranes of the rectum and ● Human rectum- 15 to 20 cm
vagina permit the absorption of many ○ Empty- contains only 2 to 3 mL
soluble drugs. of inert mucous
● EXAMPLE: ○ Resting State- rectum is not
○ Prochlorperazine & motile
Chlorpromazine ■ there are no villi or
■ For relief of nausea and microvilli on the rectal
vomiting and as a mucosa
tranquilizer ○ Has abundant vascularization
○ Oxymorphone HCl of the sub-mucosal region of
■ Opioid analgesia the rectum wall with blood and
○ Ergotamine tartrate lymphatic vessels.
■ Relief of migraine
syndrome COLONIC CONTENT
○ Indomethacin ● Systemic Effect:
■ Non-steroidal ○ Greater absorption from a
Anti-inflammatory rectum that is void from one
analgesic and that is distended with fecal
antipyretic matter.
○ Ondansetron ● Evacuation enema:
■ Relief of nausea and ○ Administered and allowed to
vomiting act before the administration of
a suppository.
● Other Conditions that influence rate
SUPPOSITORY DRUG DELIVERY vs ORAL and degree of drug absorption from the
DRUG DELIVERY rectum:
○ Diarrhea
ADVANTAGES: ○ Colonic obstruction
● Drugs destroy or inactivated by the pH ■ Tumour growth
or enzymatic activity of the stomach ○ Tissue dehydration (requires
or intestines need not be exposed to immersion in water to minimize
these destructive environments. tissue dehydration which may
● Drugs irritating to the stomach may cause irritation)
be given without causing such
irritation. CIRCULATION ROUTE
● Drugs destroyed by portal circulation ● Lower Hemorrhoidal Veins
may bypass the liver after rectal ○ Surrounding the colon receives
absorption. the absorbed drug and initiates
● The route is convenient for its circulation throughout the
administration of drugs to patient who body.
are unable or unwilling to swallow ● Lymphatic Circulation
medication. ○ Assists in the absorption of
rectally administered drugs.
pH and LACK of BUFFERING CAPACITY of ● Base irritates the mucous
the RECTAL FLUIDS membrane of the rectum
● Rectal Fluids ○ May initiate a colonic response
○ Neutral in pH and prompt bowel movement
○ No effective buffer capacity → eliminate prospect of
● Suppository Base complete drug release and
○ Influence release of active absorption
constituents ● Retention Time
○ Cocoa Butter ● Long acting or slow release
■ Melts rapidly at body suppository
temperature ○ Alginic acid
■ Immiscibility with fluids ■ Base used to prolong
● Fails to release the release of the drug
fat-soluble drugs for several hours.
readily
■ For systemic effects: SUPPOSITORY BASE
● Un-ionized ● Plays an important role in the release
(Base) of the medication.
Form-Maximize ● First requisite for a suppository
stability base.
○ Water-miscible Base ○ Should remain solid at room
■ Glycerinated Gelatin & temperature but soften, melt,or
Polyethylene Glycol dissolve readily at body
● Dissolve slowly temperature so that the drug is
and thus retard fully available soon after
release of the insertion.
drug. ● Water soluble drugs
○ Cocoa butter - Good release;
PHYSICOCHEMICAL FACTORS of the innate emolient property
DRUG and SUPPOSITORY BASE ■ Irritation or inflammation
is relieved - emollient or
● Lipid-water solubility soothing, spreading
○ A lipophilic drug that is action
distributed in a fatty suppository ● Fat soluble drugs
base in low concentration has ○ release more readily in
less tendency to escape to the glycerinated gelatin or
surrounding aqueous fluids with polyethylene glycol
hydrophilic substance in a fatty ○ Release readily in water soluble
base. type base
● Particle Size
○ The smaller the particle, the
greater the surface area,the CLASSIFICATION OF SUPPOSITORY BASE
more readily the dissolution of
the particle and the greater the 1. FATTY OR OLEAGINOUS BASES
chance for rapid absorption. ● Most frequently employed → Cocoa
butter
NATURE OF THE BASE ● Other oleaginous bases:
● Base interact with the drug ○ Hydrogenated fatty acids of
○ Inhibits release = vegetable oils
impaired/prevented drug ■ Palm kernel oil
absorption ■ cottonseed oil
 ○ Fat based compounds Wecobee
■ Glyceryl monostearate ● Triglyceride derived from coconut oil
■ Glyceryl monopalmitate
■ Combination: to achieve Witepsol
desired hardness ● Triglyceride of saturated fatty acids
● Emulsifying agent C12-C13 with varied portions of the
○ for prompt emulsification when corresponding partial glycerides.
suppository makes contact with
aqueous body fluids →
Miscellaneous base 2. WATER-SOLUBLE and
WATER-MISCIBLE BASES
a. COCOA BUTTER NF
● Fat obtained from the roasted seed of a. GLYCERINATED GELATIN
Theobroma cacao. ● Prepared by dissolving granular
● At Room temperature: gelatin (20%) in glycerine (70%) and
○ A yellowish-white solid having a adding water or a solution or
faint, agreeable chocolate-like suspension of the medication (10%).
odoro ● Most frequently used in preparation of
● Melts at 30 C to 36 C vaginal suppositories with which
● POLYMORPHISM prolonged local action of the medicinal
○ Because of triglyceride content agent is desired.
○ Existence in several crystalline ● Slower to soften and mix with
form physiologic fluids than cocoa butter →
○ Metastable Crystalline form provides slower release
(alpha crystals):
■ Results when melted at b. POLYETHYLENE GLYCOL
a temperature greatly ● Combinations of these PEG may be
exceeding the minimum combined by FUSION, using two or
required temperature more of the various types to achieve a
and is then quickly suppository base of the desired
chilled consistency and characteristic.
■ Has a lower melting ● DO NOT MELT at body temperature
point that of the original but rather DISSOLVE slowly in the
- will not solidify at room body’s fluid.
temperature. ● Do not contain more than 20% water
○ Beta Form *problem; if inserted they will attract
■ Greater stability and a water in the tissue
higher melting point. ● NOTE:
○ Phenol and Chloral hydrate ○ Advice the patient to dip in
■ Have a tendency to water just before use to avoid
lower the melting point irritation of the mucous
of cocoa butter membranes after insertion.
○ Cetyl ester wax (20%) or ■ Prevent stinging
Beeswax (4%) sensation.
■ Solidifying agent ● ADVANTAGE:
○ Solid Nature
Fattibase ■ Permits slow insertion
● Triglyceride from palm, palm kernel, without fear they will
and coconut oils melt in the fingertips.
○ Do not leak from the orifice
3. MISCELLANEOUS BASES ○ MINERAL OIL
● Mixtures of oleaginous and ■ A thin coat of oil is
water-soluble or water-miscible applied to the molding
materials. surface.
● May be chemical or physical mixtures.
● Preformed Emulsions PREPARATION BY COMPRESSION
○ Water-in-oil type ● Prepared by forcing the mixed mass of
○ Capable of dispersing in the base and the medicaments into
aqueous fluids. special molds using
● Example: suppository-making machines.
○ POLYOXYL 40 STEARATE ● Suited for making suppositories that
■ A surface active agent contains:
■ Mixture of monostearate ○ HEAT-LABILE substance
and distearate esters of ○ INSOLUBLE substance in the
mixed polyoxyethylene base
diols and the free ■ Permits no likelihood of
glycols. insoluble matter settling
■ Average polymer length during manufacture
equivalent to about 40 ● DISADVANTAGE:
oxyethylene units. ○ Special suppository machine is
■ Melting Point: 39 C to required and there are some
45 C limitations as to the shapes of
suppositories that can be
PREPARATION OF SUPPOSITORIES made.
● MOLDING FROM A MELT
● COMPRESSION
● HAND ROLLING AND SHAPING PREPARATION BY HAND ROLLING AND
SHAPING
● Historic part of the art of the
PREPARATION BY MOLDING pharmacists.
STEPS: ● With ready availability of suppository
● Melting the base molds of accommodating shapes and
● Incorporating any required sizes, there is little requirement for
medicaments today’s pharmacist to shape
● Pouring the melt into molds suppositories by hand.
● Allowing the melt to cool
● Removing the formed suppositories Examples of Suppositories
from the mold 1. URETHRAL SUPPOSITORIES
● Example of base suitable for ● Thinner and tapered, about 5 mm in
molding: diameter.
○ Cocoa butter ● Example:
○ Glycerinated gelatin ○ ALPROSTADIL (Muse)
○ Polyethylene glycol ○ Single use medicated
transurethral system for the
LUBRICATION OF THE MOLD delivery of alprostadil to the
● Lubrication before the melt is poured to male urethra.
facilitate clean and easy removal of the ○ Suspended in a polyethylene
molded suppositories. glycol 1450 excipient and is
● Cocoa butter does not need lubrication formed into a medicated pellet
● LUBRICATION IS NECESSARY: → microsuppository
○ GLYCERINATED GELATIN
 measuring 1.4 mm in diameter ● Glycerinated Gelatin
and 3 or 6 mm in length. ○ Stored at controlled room
○ USE: Treatment of erectile temperature (20°C to 25°C, or
dysfunction. 68°F to 77°F).
● Suppositories are also commonly
2. VAGINAL SUPPOSITORIES packaged in slide boxes or in plastic
● Employed principally: boxes.
○ To combat infections in the ● Suppositories stored in:
female genitourinary tract. ○ High humidity may absorb
■ Ex: Anti-infectives moisture = SPONGY
○ To restore the vaginal ○ Extreme dryness = lose
mucosa to its normal state moisture and become BRITTLE
■ Ex: Estrogenic
substance VAGINAL INSERTS
○ For contraception. ● AKA: Vaginal tablets
■ Ex: Nonoxynol-9 ● Usually ovoid and are accompanied in
● Buffered to an acid pH usually about their packaging with a plastic inserter
4.5 → normal vagina (a device for easy placement of the
tablet within the vagina)
● Contain the same types of
How To Administer? anti-infective and hormonal substances
as vaginal suppositories.
● Some are capsules of gelatin
containing medications to be released
intravaginally.
● Prepared by: Compression

MEDICATION STICKS
● Are cylindrical in shape and generally
range from 5-25g
PACKAGING and STORAGE
● Packaged in an applicator tube for
● Packaged in TIGHTLY CLOSED glass
topical administration and the
containers prevent a change in
applicator can be adjusted to
moisture content.
continually expose new, fresh sticks
● Cocoa butter base:
from the inside tube.
○ Usually
● Prepared similar to suppositories
○ individually wrapped or
except that the melt is poured into
otherwise separated in
administering device, or tube.
compartmented boxes to
● Example: Acyclovir Lip Balm
prevent contact and adhesion.
○ must be stored below 30°C
[END]
(86°F), and preferably in a
refrigerator (2°C to 8°C, or
36°F to 46°F).
● Light Sensitive Drugs:
○ Individually wrapped in an
opaque material such as a
metallic foil.
● Polyethylene Glycol
○ Stored at usual room
temperatures.
 SOLUTIONS ● Colloidal Solution
−7
○ particle size between 10 cm
SOLUTIONS −5
Main Examples of solutions and 10 cm
● Syrup - Sugar + water ● Suspensions
−5
● Elixir - Sugar + water + alcohol ○ Particle size greater than 10
● Spirit - Aromatics + water + alcohol cm
● Aromatics - Aromatics + water
● Tincture - Extractives + water/alcohol
(hydroalcoholic)
*Elixirs can either be medicated or
nonmedicated.
*Aromatics are composed of volatile oils
*water/alcohol = hydroalcoholic

Challenge yourself ● Chemical substances dissolved in a

● What is the greatest advantage of suitable solvent or mixture of mutually
solutions? miscible solvents
a. Very stable ● Homogenous
b. Highly palatable ● ROA: oral, otic, ophthalmic, topic
c. Fast Absorption
d. Preferred by any age group
Pros & Cons of Pharmaceutical Solutions
● What is the rate-limiting step in ● Advantages
absorption? ○ Rapid drug action
○ Dissolution ○ Rapid drug absorption
○ Dose uniformity - depends on
● What is the most preferred solvent in the quality of the preparation
pharmaceutical solutions? ○ Volumes of liquid can be
○ Water (major component of measured accurately
solutions) ○ Easy to swallow
○ Easy to manufacture than other
● How do you describe a co-solvent? DF’s
○ “Auxiliary solvents” ● Disadvantages
○ Another kind of solvent that ○ Many drugs are already
makes the preparation more unstable - increased instability
soluble if in solution
○ Poorly soluble drugs not
suitable
○ Bulky!
○ Packaging materials is more
costly
*Risk of underdose or overdose

Important concepts about solvency

Solutions
● True Solution
−7
○ Particle size less than 10 cm
 Ordinary drinking water from the tap is NOT
acceptable for the manufacture of most
aqueous pharmaceutical preparations or for
the extemporaneous compounding
prescription.

DISTILLATION

● OH/Hydroxyl groups - improve

solubility
● Greater # of POLAR group, greater ION
solubility in WATER
● INCREASE IN MW OR ORGANIC
compound and without change in
polarity REDUCES SOLUBILITY IN
WATER
● SALTS of organic compound are more
SOLUBLE IN WATER EXCHANGE TREATMENT
○ Salts are ionized therefore they REVERSE OSMOSIS
dissolve better in water
● ORGANIC bases are more SOLUBLE
in ORGANIC SOLVENTS

Common SOLVENTS for Liquid Preparations

Type of Water Use

Purified water Used for the preparation of

medicines that do not have to be
*Obtained by sterile and apyrogenic ● Microfiltration - bacteria
distillation, ion ● Ultrafiltration - virus
exchange treatment, *Does not contain more than 1%
reverse osmosis*, or solids ● Nanofiltration - organic compounds
other suitable process *Hard water - contains Mg and Ca (300 - 1,000 MW)
● Reverse osmosis (particles <0.001
Highly purified Used for the preparation of um)
Water medicines where water of high ○ Reverse osmosis removes
biological quality is needed,
except where water for injections virtually all viruses, bacteria,
are required. pyrogens, and organic
molecules and 90% to 99% of
Water for injection Used for medicines for parenteral ions
administration. *pyrogens - fever inducing
MUST BE PYROGEN FREE.
OTHER SOLVENTS BESIDES WATER
Sterilized water for Used for medicines for parenteral
Injection administration. ● Alcohol, USP
○ Next useful solvent to water;
Water has been sterilized by
HEAT and is suitably packaged 94.4% to 96% v/v @ 15.56°C
● Dehydrating Alcohol, USP
○ “Water-free alcohol”, NLT
NOTE: 99.5%
 ○ Used with other solvents like
formulations
glycols and glycerin to reduce
amount of alcohol required Sweetening agent in ≦20
● Dilutes alcohol (50%) alcoholic elixirs
○ Equal amount of Alcohol, USP
and Purified Water
○ Final volume contracts by 3% ● Propylene glycol
● Rubbing alcohol ○ Viscous, miscible with water
○ 70% alcohol and alcohol
○ Must have denaturant (sucrose ○ Used as auxiliary solvent
octaacetate or denatonium
benzoate) Alcohol Limits for OTC Oral Products
○ *Example: Isopropyl alcohol ● <6 yr. Old - 0.5%
and ethyl alcohol ● 6-12 yr. Old. - 5%
○ Denaturants - renders rubbing ● >12 yr. Old - 10%
alcohol unfit for drinking

● Glycerin, USP (Glycerol) USUAL COMPONENTS OF A

○ Clear syrupy liquid with a sweet PHARMACEUTICAL SOLUTION
taste, less viscous with heating ● Active ingredient
○ Used as stabilizer and ○ Solubility is a must
auxiliary solvent ○ Provides the therapeutic effect
○ Some therapeutic uses of ● Solvent
glycerin: Humectant ○ Must dissolve the API and must
be suitable for the ROA
● Others
Uses of glycerin ○ Colorants, Flavorants,
Sweeteners
Use Concentration (%)
■ Important for
Antimicrobial <20 palatability of oral
preservative solutions
○ Preservatives, Antioxidants,
Emollient ≦30 Chelating agents,
pH/isotonicity adjusters
Gel vehicle, aqueous 5.0-15.0 ■ Generally improves
stability and
Gel vehicle, non 50.0-80.0 compatibility of the
aqueous product

humectant ≦30 Challenge Yourself

Excipient Function
Ophthalmic 0.5-3.0
formulations Mannitol Sweetening agent

Patch additive Variable Propylene Glycol Co-solvent

Plasticizer in tablet Variable Disodium EDTA Chelating agent/ Complexing

agent/Sequestering agent
film coating
Citric Acid Acidifying agent
Solvent for ≦50 Antioxidant
parenteral Isotonicity adjuster
 Preservatives Parabens (methyl, propyl. butyl)
(antifungal)
Ascorbic Acid; Antioxidant
Benzyl alcohol - preservative in
Isotonicity adjuster parenterals that can cause Gasping
Syndrome in neonates
Preservatives
Antioxidants Sodium metabisulphite, sodium
Carbomers Emulsifier sulphite, sodium bisulfite, ascorbic acid,
Viscosity enhancer used to stabilize solutions.
Thickening agent
*BHT and BHA - antioxidants; bad
reputation of being cancerous (however
it was clarified that it was NOT
COMMON EXCIPIENTS IN PHARMACEUTICAL SOLUTIONS
cancerous)

Excipients Examples of Excipients Chelating Disodium edetate, used to increase

Agents solution stability
Co-solvents Ethanol, glycerol, propylene glycol.
*The concentration of ethanol should pH Adjusters Acids, e.g. citric acid, buffers
be limited as it exerts a Alkali, e.. Sodium hydroxide, buffers.
pharmacological action following oral
administration. Isotonicity Sodium chloride, potassium chloride,
Adjusters mannitol, dextrose, glycerol
Flavouring Used to mask the taste of drugs, many
Agents of which have a very unpleasant taste. Viscosity Hypromellose, hydroxyethylcellulose,
Synthetic or naturally occurring enhancers polyvinyl alcohol, povidone, dextran,
flavorings such as Vanilla, raspberry, carbomer 940
orange oil, lemon oil are used for oral
solutions.
Preparation of Pharmaceutical Solutions
Menthol is used in both oral and nasal ● Simple Mixing
solutions.
○ Use of mixing tanks
Certain flavors appeal to certain patient ○ With or without heat
populations and certain parts of the ● Clarification
world; this must be borne in mind by ○ Use of industrial filters or
the formulator. For example, fruit and
bubble gum flavors are acceptable to
centrifuge
children, whilst mint flavor is not. ○ Remove unwanted solid
particles from fluids
Colouring A coloring agent should correlate with ● Filling and Packaging
agents the flavoring ○ Narrow-mouthed bottles
Example: green with mint, red with
cherry, like flavors, color preferences Common forms of oral solutions
varies between cultures. 1) Dry mixtures for solution - for
“reconstitution
Sweeteners Sucrose, sorbitol, mannitol, saccharin - Solutions remain stable when
sodium, xylitol, high fructose corn syrup
stored in the ref for the labeled
*for diabetic patients: aspartame, period usually 7-14 days
saccharin

Antimicrobial Used to preserve multi dose

Preservatives preparations.

Example: Benzalkonium chloride

(antibacterial), benzyl alcohol
,chlorobutanol, thimerosal,
 2) Oral solution - ready-to-take Challenge yourself
3) Oral rehydration solution (ORS) 1-2 excipients components of a syrup?
- 45 mEq Na+, 20 mEq K+, 35 ● Sugar - usually sucrose or sugar
mEq Cl-, 30 mEq citrate, and substitute
25 g dextrose ● Antimicrobial preservatives
● Flavorants
EXAMPLES OF ORAL SOLUTIONS IN THE ● Colorant s
MARKET *if below 60% - need to add preservative
Magnesium citrate
● Prepared by chemical reaction of Mg What is the important rule in choosing
carbonate and citric acid flavorant-colorant combination?
● Colorless to slightly yellow clear ● Colorant must complement the
effervescent liquid having a sweet, flavorant. Ex. Mango flavor - color
acidulous taste and lemon flavor yellow
● Keep the bottle on its side so the cork
or rubber liner of the cap is kept moist USUAL COMPONENT OF A
and swollen, thereby maintaining the PHARMACEUTICAL SYRUP
airtight between the cap and the bottle
● Active ingredient
Magnesium citrate oral solution ○ *optional
Therapeutic use: saline laxative ○ Provides the therapeutic effect
Sodium citrate and citric acid ● Solvent
● Systemic alkalinizer - useful for ○ Water + co-solvent
patients with uric acid and cystine ● Sugar
calculi of the UT ○ Usually sucrose or sugar
● Useful adjuvant with uricosuric agents substitute
in gout therapy. ● Others
● Urates tend to crystallize out of an acid ○ Colorants, Flavorants,
urine Sweeteners
■ Important for
SYRUP: A SWEETENED SOLUTION palatability of oral
solutions
Syrup, USP ○ Preservatives, Antioxidants
● Aka simple syrup ■ Generally improves
● 85% w/v (65% v/v); specific gravity stability and
1.313 compatibility of the
● Does not need preservative if used product
soon
Sugar Antimicrobial Flavorants and
Sorbitol solution, USP - 64% w/v preservative colorants

Flavored syrups:
a. Cherry syrup - uses cherry juice 47%
b. Raspberry syrup - uses raspberry
juice 48%
c. Cocoa syrup - good for bitter tasting
drugs
d. Orange syrup - uses sweet orange
peel tincture, citric acid for flavor and
tartness
- Usually sucrose - Benzoic acid - Small amount
● Better able than aqueous srups to
- Others: sorbitol, 0.1% to 0.2% of alcohol is maintain both water-soluble and
glycerin, and - Sodium added to a syrup alcohol soluble components
propylene glycol benzoate 0.1% to ensure the ● Elixir with high alcohol content usually
-Non-glycogeneti to 0.2% continued uses an artificial sweetener
c substitute - Various solution of poorly ● 10% - 12% of alcohol are usually
- methylcellulose combinations of water-soluble self-preserving
or methylparaben, flavorant (e.g. ● Prepared by simple solution
hydroxyethylcellu propylparabens volatile oil, ● Aqueous solution is added to the
lose , and vanillin)
alcoholic solution rather than the
- Has a soothing butylparabens - Colorant should
effect on irritated totaling about always correlate
opposite
tissue of the 0.1% with the flavorant ● Expect cloudy final mixture- let it stand
throat to ensure saturation
- Self-preserving ● Talc can be added as filter aid and/or
effect other co-solvents can be added ( but
this adds to the viscosity and slows the
rate of filtration)
Preparation of Syrups
● With heat
○ prone to sugar inversion Non-medicated Medicated
● Agitation w/o heat
- pleasant - Antihistamine elixirs
○ good for heat sensitive -tasting vehicle or to dilute - mostly are basic amines.
components, slow process an existing medicated elixir They are rendered
● Addition of sucrose ● Should have the water-soluble by interaction
○ useful in preparation of tincture same alcoholic with acid.
concentration with - Phenobarbital elixir
or fluidextract
the elixir being - 0.4% or 20 mg of drug per
● Percolation - used in Ipecac syrup* diluted 5ml; commonly flavored with
○ Consists of the dried rhizome - Color and flavor should not orange oil, colored red and
and roots of Cephaelis be in conflict with those of sweetened; minimally, 14%
ipecacuanha medicated elixirs. alcohol keeps the drug
- Examples: aromatic elixir, dissolved
○ emetine , cephalinem and compound benzaldehyde - Digoxin elixir
psychotrine extracted by elixir and iso alcoholic elixir - uses 10% alcohol
hydroalcoholic solution
*percolation is the most preferred method.
*Ipecac syrup - used to induce vomiting
TINCTURES
(emetic)
● Alcoholic/hydroalcoholic solutions
prepared from vegetable materials or
Important concepts about syrups
from chemical substances
● Sucrose may be hydrolyzed into
● 15% to 80% alcohol (preservating and
dextrose (glucose) and fructose
solubilizing)
(levulose
● Compound benzoin tincture will
● Invert sugar is sweeter and darker ⟶
precipitate out its alcohol-soluble
amber colored (caramelized)
principles upon addition of water
● This decomposed syrup is more
● Examples: Paregoric, USP or
susceptible to fermentation and to
camphorated tincture of opium
microbial growth
● Opium tincture, USP or Laudanum
OTHER SOLUTIONS IN THE MARKET
Proper Administration and Use of Liquid
ELIXIRS
Peroral Dosage Forms
● Clear, sweetened hydroalcoholic
● Measure out the dosage in calibrated
solution
devices
 ● Drink a glassful of water after intake
● Syrups may not be suitable for Hydrogen peroxide topical solution
diabetics ● Prepared by (1) reaction of phosphoric
● Don't give elixir to a patient taking or sulfuric acid on barium peroxide (2)
Metronidazole and Chlorpropamide electrolytic oxidation of conc. Sulfuric
○ Disulfiram-like effect acid to form persulfuric acid which
(hangover) hydrolyzes to H2O2
● 3% or 10 volumes; 6% or 20 volumes
TOPICAL SOLUTIONS AND TINCTURES ● Works by releasing nascent oxygen on
Prepared By: contact with tissues; cleanses wounds
1. Simple Solution by mechanical action through bubbling
2. Chemical Reaction and frothing
3. Maceration - soaking ● Uses acetanilide as preservative

SPRAYS - aqueous or oleaginous solutions in Chlorhexidine gluconate solution

the form of coarse droplets or finely divided ● Broad spectrum antiseptic
solids. ● 0.12 % CG is the FIRST RX- ONLY
Ex. Atomizer - form of fine droplets antiplaque, antigingivitis drug with
Examples of topical solutions in the market antimicrobial activity
● Aluminum acetate soln - aka Thimerosal Solution
BURROW’S SOLUTION ● Water soluble organic mercurial,
● Calcium hydroxide soln - aka LIME bacteriostatic and mild fungistatic
WATER, LIQUOR CALCIS ● 0.1 % THIMEROSAL- Uses ED and
● Coal tar Topical Soln- aka LIQUOR sodium borate to maintain alkalinity
CARBONIC DETERGENS, LIQUOR required for stability
PICIS, CARBONIC , LCD Povidone Iodine Solution
○ Local anti-eczematic ● Chemical complex of iodine with PVP
○ 20% coal tar, 5% polysorbate → slow release of 10% iodine
80*
○ Mixed with washed sand and Example of Topical Tinctures in the Market
alcoholic solution
Iodine tincture
Challenge Yourself ● Iodine crystals and sodium iodide in
A nearly black viscous liquid having a hydroalcoholic vehicle (forms iodine
characteristic naphthalene-like odor and a triiodide)
sharp, burning taste. It is a byproduct during Compound benzoin tincture
the destructive distillation of bituminous coal. ● 10% benzoin, aloe, storax, and tolu
a. Thimerosal balsam
b. Coal tar ● Protectant and inhalant; delivery
c. Chlorhexidine gluconate vehicle of podophyllum in the tx of
d. Burow’s solution venereal warts
● Synonyms: Friar Balsam’s, Turlington’s
Merthiolate is the brand name of? drop, Persian balsam, Swedish
a. Benzalkonium chloride balsam, Jerusalem balsam, Waddes
b. Thimerosal drop, and Turlington’s balsam of life.
c. Chlorhexidine gluconate Thimerosal tincture
d. Povidone-iodine ● Decomposed by metals thus should be
e. A and B prepared and stored in glass
● Monoethanolamine and
6% Hydrogen Peroxide = 20 volumes ethylenediamine can be used as
3% Hydrogen Peroxide = 10 volumes stabilizers
 ● Orange red with greenish fluorescence l topical astic
soln
Summary Of Topical Solutions And
Tinctures Hydrogen _ 3% Aqueous Topical
Peroxide anti-infecti
Examples of Solutions Applied to the skin ve

Hydroquin Melanex 3% Water, Temporar

Soln Commer Active Vehicle Category one topical alcohol y
cial soln constit soln PEG bleaching
uent of
hyperpig
Aluminum _ 5% Aqueous Astringent mented
acetate skin
Aluminum _ 2.5 % Aqueous Astringent Ketoconaz Nizoral 1% Water Tx for
Subacetate AlO ole A-D dandruff
5.8%
Acetic Minoxidil Rogaine 2.5 % Alcohol , Tx for
acid Topical water baldnes
soln PEG
Calcium _ 0.14% Aqueous Astringent
Hydroxide Povidone Betadine 7.5 - Aqueous Topical
(lime Iodine soln 10 % infective
water)
Tolnaftate 1% PEG Topical
Chlorhexidi Hibiclens 4% Skin antifungal
ne skin wound &
gluconate Cleanser general Undecyleni 25% Oil base Topical
skin c acid antifungal
cleanser

Clindamyci Cleocin 1% Isopropy Tx for Examples of Tincture Applied to the skin

n T Topical l acne
Phosphate Soln Alcohol, vulgaris
water Tincture % Vehicle Category
Active
Clotrimazol Lotrimin 1% PEG Antifungal Constitu
e soln 400 ent

Coal Tar _ 20 % Alcohol Antiecze Green soap 65 % Alcohol Detergent

matic: Tincture Contains 2%
Antipsoria lavender oil
tic
Iodine 2% Alcohol, Topical Anti
Erythromyc Erymax 2% PEG Tx Acne tincture water infective
in topical Acetone vulgaris
soln ( , alcohol Compound 10% Alcohol Topical
alergan) benzoin benzoin Protectant
tincture 2% aloe
Fluocinolo Synalr 0.01 PEG Adrenoco 8%
ne Topical % rtical storax
acetonide soln steriod 4% Tolu
balsam
Fluorouraci Efudex 2.5 % PEG Antineopl
Podophyllin Podoco Benzoin Removal of
 n- 25 in soft genital
LINIMENTS
tincture wax Liniment - alcoholic or oleaginous or
emulsion prep “intended to be rubbed”
● Alcoholic or hydroalcoholic - as
Vaginal and rectal solution rubefacient, counterirritant or
1. Vaginal douche penetration is desired
● used for hygiene ● Oleaginous- as massage; less irritating
2. Retention enemas *liniment - causes reddening and irritation; kill
● used to minimize undesirable the pain but the source of pain is still there
GI reactions associated with *rubefacient
oral therapy.
● Example: Aminophylline Challenge yourself
3. Evacuation enemas What acids are used in the preparation of
● used to cleanse the bowel collodion?
● Examples: solutions of sodium a. Hydrochloric acid and nitric acid
phosphate and biphosphate, b. Hydrochloric acid and sulfuric acid
glycerin, docusate K, and LMO c. Sulfuric acid and nitric acid
SuNi (1:1)
OTHER SOLUTIONS: d. Sulfuric acid and acetic acid
SPIRITS
● Alcohol or hydroalcoholic solution + COLLODIONS
volatile substance ● Pyroxylin, nitrocellulose, soluble
● Usually more than 60% alcohol gun cotton, collodion cotton.
● As flavoring agent or medicated spirit ● Obtained by the action of a mixture of
● Prepared by simple solution, sulfuric and nitric acids (1:1) on cotton
maceration, or distillation (consists chiefly of cellulose
● Example: aromatic ammonia spirit, tetranitrate)
compound orange spirit, peppermint ● Clear or slightly opalescent viscous
spirit liquid prepared by dissolving pyroxylin
*Aromatic ammonia spirit - smelling salts, (4% w/v) in a 3:1 mixture of ether
administered via inhalation; used to prevent or and alcohol.
treat fainting ● Useful in holding edges of an incised
wound together , but uncomfortable
AROMATIC WATERS because of inflexible nature
● Water + volatile substance ● Highly volatile and flammable
● Used to perfume or flavor Applicator: camel’s hair brush or glass
● Example: peppermint water, camphor applicator
water NF, caraway water, rose
aromatic water, etc.
DILUTED ACIDS Flexible collodion
● Water + concentrated acid (%w/v) ● Camphor - 2% - waterproofing
● Example: Acetic acid- antibacterial in ● Castor oil - 3%- flexibility or
surgical dressings 1% spermatocidal, plasticity
irrigation solution for bladder (0.25%)
Salicylic Acid Collodion
What is the main difference between a gargle ● 10% salicylic acid in flexible collodion
and a mouthwash? ● Keratolytic
Gargle - throat ● One drop at a time application, line the
Mouthwash - mouth cavity only healthy skin with whitw petrolatum to
avoid irritation
NON-AQUEOUS SOLUTIONS:
Extraction terms ○ Extraction and evaporation by
● Menstruum - solvent or solvent the menstrua/ solvent makes
mixture “extracts” very potent (mainly
○ Hyroalcoholic is the most composed of the active art of
versatile and most used, with the drug)
inherent preservative power ○ Uses percolation method →
and prevents separation of distillation
extractives upon standing ○ Three forms:
○ Glycerin can be a co-solvent of 1. Semi-liquid or syrup
water and alcohol 2. Pilular or solid (plastic
● Marc - plant residue after actives are consistency) for
removed ointment and paste
3. Powdered - for
powders, capsules,
tablets

Syrup water + sugar Aqueous solution

of sugar

Elixir Water + alcohol + Sweetened

sugar hydroalcoholic
solution
What are the two main methods for
extraction? Spirit Water + aromatics Hydroalcoholic
● Process P (Percolation) + alcohol solution of
● Process M (Maceration) volatiles

Aromatic Water + aromatic Aqueous solution

EXTRACTION METHODS Waters substance of volatiles
1. Maceration - Process M
● “Soak” - comminuted drug is allowed Tincture Extracting active Hydroalcoholic
to soften, penetrated by the constituents from solution of
crude drugs vegetable
menstruum.
(water and/or material; variable
● 15 C - 20 °C for 3 days alcohol) conc.
● Preferred for Benzoin, Tulo and Aloe
Fluidextract Extracting active 1 g of drug per 1
2. Percolation - Process P constituents from mL
crude drugs
● “Strain” - slow passage of solvent (water and/or
through a column of drug alcohol)
● Preferred for: Coffee

EXTRACTIVES: Special topic: Ophthalmic sterile solution

● FLUIDEXTRACTS ● Anesthetics - “caine”
○ Liquid preparations of ● Antibiotic and antimicrobial agents
vegetable drugs prepared by ● Antifungal agents
percolation ● Anti-inflammatory agents - allergic
○ 1g of drug per 1 mL conjunctivitis
○ 100% extract ● Antiviral agents
● Astringents - for conjunctivitis - zinc
● EXTRACTS sulfate
○ Concentrated preparations of ● Beta-adrenergic blocking agents -
vegetable or animal drugs intraocular pressure and open-angle
glaucoma
 ● Miotics & other glaucoma agents ● Emulsions = liquid in liquid
● Mydriatics & cycloplegics ● Gels and Magmas = Colloidal
● Protectants and artificial tear - dispersions
celluloses ● Aerosols = gas in gas
● Vasoconstrictors and ocular
decongestants- “zoline” *dispersed medium = large amount
*dispersed phase
Requirements: Ophthalmic sterile solution
● Sterility Challenge yourself
○ Use of bacterial filters or What of the following consists of two
autoclaving immiscible liquid phase?
● Preservation a. Suspension
○ Benzalkonium chloride (0.01%) b. Emulsions
and either Polymyxin B sulfate c. Solutions
(1,000 USP U/mL) or disodium d. gels
EDTA (0.01%-0.1% are
effective against most strains of Suspensions vs Emulsions
Pseudomonas. Suspensions Emulsions
● Isotonicity - osmotic equivalent of
0.6% to 2% has no marked discomfort INsoluble particles IMmiscible liquid
to the eyes. dispersed in a liquid dispersed in another
○ Boric acid 1.9% same osmotic vehicle liquid
pressure as 0.9% sodium
chloride. A good suspension will A good emulsion will
● Buffering appear HOMOGENEOUS appear
○ pH of normal tears is about 7.4 HOMOGENEOUS
● Viscosity Contains a SUSPENDING Contains an
○ Optimal in the range of 15 to 25 agent (3rd component) EMULSIFYING agent
cP 0.25% methylcellulose of
4000 cP or hydroxypropyl
methylcellulose and polyvinyl SUSPENSIONS
alcohol. ● Dispersions of insoluble solid
● Ocular Bioavailability materials, generally, the drug in a liquid
○ Cornea is best permeated by form.
drugs with both lipophilic and ● The most important consideration in
hydrophilic characteristics. suspension formulation development is
● Packaging - usually in plastic eyedrop the interaction between the solid
container particles and the liquid vehicle
○ Ophthalmics should be ● Formulator concern:
sparkling clear and free of all ○ Decrease rate of settling
particulate matter, have ○ Easy resuspendability
micronized particles.
○ For suspension from, they Desirable Properties of a Suspension
should not aggregate and must 1. A properly prepared pharmaceutical
easily redistribute upon gentle suspension should settle slowly and
shaking. should be readily dispersed upon
gentle shaking of the container.
DISPERSED SYSTEMS 2. The particle size of the suspensoid
should remain fairly constant
Main examples of Disperse Systems throughout long periods of undisturbed
● Suspensions = Solid in liquid standing.
 3. The suspension should pour readily What is the downside of having very fine
and evenly from its container particles for suspensions?
a. They form a hard cake
Challenge yourself b. They form a network of loose
In most good pharmaceutical suspensions, aggregates
the particle diameter is ____. c. They tend to float on the surface
a. Less than 1 um d. They dissolve in the medium
b. 1 to 50 um
c. 50 to 100 um Important concepts
d. More than 100 um ● Suspensions are not optically clear
and will appear cloudy unless the size
Coarse dispersions - particle size is 10-50 of the particles is within the colloidal
um (suspension and emulsions) range.
Colloidal dispersions - magmas and gels ● Electrical double layer theory
Fine dispersion - particle size is 0.5 to 10 um explains solid particle-liquid vehicle
interaction
STOKES EQUATION vs STOKE- EINSTEIN
EQUATION

Where:
Rate of sedimentation (or creaming) (v)
*negative v = creaming
*positive v = sedimentation

Viscosity (n) Considerations for suspension formulation

Radius of particle (a) - has the highest effect ● Wettability
in terms of sedimentation rate ● Particle interaction behavior
Density of particle (P1) ● Electrokinetics
Density of medium (P2) ● Aggregation
● Sedimentation

Wettability or wetting property

● Hydrophilic substances - easily
wetted by water or polar liquids, can
increase viscosity of water
Where: suspensions.
Diffusion coefficient (D) ● Hydrophobic substances- repel water,
Viscosity (n) easily wetted by non polar liquid.
Radius of diffusing particle (a) ○ Requires wetting agent or use
of surfactants - decrease
Challenge yourself solid-liquid interfacial tension
Which one of the following defects is ○ Use of dispersing agents
caused by negative velocity? (hydropholoc polymers) - Na
A. Creaming CMC, bentonite, colloidal silica
B. Precipitation ○ Lanolin derivatives can also
C. Breaking improve wetting
D. Inversion
 *Lyo - solvent
*Hydro - water
*Lyophobic - afraid of solvent
*Hydrophobic - restricted to water

Particle interaction and behavior and

Electrokinetics
● Lyophobic - nonwetting, sensitive to
(+) salts
● Lyophlic - wetting, e.g., gum → large
amounts of electrolytes → salting out A. Deflocculated
effects → reversible precipitation with B. Flocculated
dilution
● Schulze-Hardy rule - valence of the
ions having a charge opposite to that
of hydrophobic particles determines Flocculated Deflocculated
the effectiveness of electrolyte in
particle in particle aggregation - Aggregates - Individual fine
● The aggregation value or efficiency - Higher particles
increases with the valence ions. sedimentation height - Low sedimentation
- Redispersible height
Aggregation Phenomena - Prone to caking

Floccule/ open Coagulate/ Disaggregated

network Closed or dispersed
aggregate aggregate form

- aggregates - tight packing -individual

settle quickly arising from particles are
(because it is surface film dispersed as
heavy) bonding discrete entities
- redispersible -low sediment - lowest possible
- far apart to avoid height sediment height
caking -not easily - crystal bridging
redispersed → leads to caking

● The F value of an ideal suspension is

1.

Important terms related to suspensions

SEDIMENTATION ● Caking - formation of nonredispersible
sediment within a suspension system
○ Caused by crystal bridging and
closed aggregation
● Crystal bridging - particle surface
crystal growth occurs on two or more
particles simultaneously and results in
a steady formation of crystal-linked
particles.
 ● Crystal habit - outward appearance of
an agglomeration of crystals
● Subsidence - settling of an
aggregated system and refers to the
settling rate.
● Ostward ripening - small particles in
suspension seem to disappear and
large particles grow after repeated
temperature changes in both directions
*Repeated temperature cycling aggravates Suspending agents
this situation, with the result that the smaller ● make the preparation thicker and this
particles dissolve completely and larger suspends the suspensoid
particles grow ● Examples: carboxymethylcellulose
(CMC), methylcellulose,
microcrystalline cellulose,
polyvinylpyrrolidone, xanthan gum, and
bentonite

*representation of Ostwald ripening in Challenge yourself:

suspension What happens if you add too much
suspending agent?
a. Easier pourability
What is a bad suspension? b. Lower suspendability
c. Higher stability
d. Lower pH
What will happen if there is too much
lubricant?
- Decrease dissolution
Remedy: Sodium Lauryl Sulfate (SLS) -
surfactant
- Break the surface tension therefore it
will improve the penetration
1st pic - caking/sedimentation/subsidence
2nd pic - floc/flocculate What is the study of flow and deformation of
3rd pic - creaming/floatation solids?
- Rheology (study of flow of liquids,
Usual components of a pharmaceutical AND deformation of solids)
suspension
● Suspending agent Wetting agents (OH groups)
● Dispersing agent ● Alcohol, glycerin, and propylene glycol
● Wetting agent are employed as wetting agents when
● Others: colorants, flavorants, and an aqueous vehicle is to be used as
preservatives the dispersion phase.
ROLES of each ingredient:
● Aluminum hydroxide compressed gel -
● Sorbitol solution
● Syrup *bottom-top approach (spray-drying)
● Glycerin
● Methylparaben - preservatives ● If suspension is prepared via controlled
● Propyl paraben - preservatives crystallization, a supersaturated
● Flavor - flavorant solution should be formed then quickly
● Purified water, to make - vehicle cooled with rapid stirring → formation
of many nuclei → many crystals
Techniques for suspension preparation
● If suspension is prepared via
dispersion process, pulverization of
solid is best achieved by:
1) micronization (top-bottom
approach)
2) spray-drying (bottom-top
approach)

*least frequently used (ultrasonic equipment)

*top-bottom approach (micronization)
SUMMARY OF SUSPENSION
MANUFACTURE

Hydrocolloid is disposed in water at recommended

temperature based on suspending agent using a
blender

Foam is formed → Allow hydrocolloid to be

suppress using sufficiently hydrated
anti-foaming agent
 ↓ ● Permits administration of liquid drug in
globules than in bulk
Dilute hydrocolloid and add active ingredients using ● Oral emulsion - palatable
propeller. administration (by masking)
○ Ex. Cod liver oil
Add remaining water-soluble ingredients pre-dissolved
in water followed by oil-soluble flavor. Use a
● Topical emulsion - can be emollient
dispersator. (W/O), can mask irritating drugs in
internal phase (IP)
↓ ● Topical absorption can be enhanced
due to reduced particle size of IP
Add enough solvent to make the final volume.
Types of Emulsions

Oil in water (O/W)

● Suitable for IV route and oral route
○ Parenteral nutrition
○ Drug carriers
● Low viscosity
Examples of suspensions in the market ● Medicinal oils for constipation, oral
● Kaolin mixture with pectin - food supplements, vitamins
Kapectolin®, Kao-Pec®, Kao-Pect®
● Aluminum hydroxide, magnesium
carbonate (contrasting)
○ What happens if you only take Water-in-Oil (W/O)
either of the two? ​ ● Suitable for topical route and subQ/IM
→ Aluminum (constipation) injections
“Ala Tae” ● Dermatologic emulsions usually use
→ Magnesium (diarrhea) “Mag ionic or non ionic surfactants
Tatae” ● High viscosity
● Bismuth subsalicylate -
Pepto-bismol®, Kaopectate® Multiple Emulsions (O/W/O or W/O/W)
● Barium sulfate for Suspension, USP - ● rate-controlled release
contrast agent
Challenge yourself
Packaging and Storing Suspensions Thermodynamically stable, optically
● Extemporaneous - airtight, transparent isotropic mixtures of biphasic
light-resistant, refrigerated O/W system stabilized with surfactants.
● “Shake well” label a. Fluid Extract
● Watch for consistency or color change b. solutions
● Wide-mouthed with enough airspace c. Microemulsion
above liquid d. emulsion
e. NOTA
EMULSIONS
● Allows prep of relatively stable and Nanoemulsions vs Microemulsions
homogeneous mixture of two
immiscible liquids
 Emulsifiers (w/o) 3-6

Wetting agents 7-9

Emulsifiers (o/w) 8-18

Solubilizers 15-20

Detergents 13-16

Nanoemulsions Microemulsions Wetting Agents based on Charge

● Anionic surfactant
Thermodynamically Thermodynamically stable ○ SLS, Sodium stearate - O/W
UNstable
○ Calcium Oleate - W/O
Optically clear and Optically clear and ● Cationic surfactant
transparent optically clear transparent ○ Quaternary Ammonium
and transparent compounds (cetrimide) - O/W
*quaternary compounds are cationic; soluble
Dispersions of oil and Isotropic mixtures of a
water (as individual biphasic o/w system in water (ionized)
droplets) (Ansel’s) *example: ammonium compounds
*ionized = water soluble
single -phase system, “not ● Non- ionic
emulsion” (Aulton’s) ○ Spans (Sorbitan) - W/O
○ Tweens (POE sorbitans) - O/W
*Polyoxyethylene (POE)
○ Cetomacrogol - O/W
● Polymeric
○ Pluronics (poloxamers) - O/W
Which of the following is/are correct about
surfactants with high HLB (Hydrophilic ● Fatty amphiphiles
Lipophilic Balance) values? ○ Cetyl alcohol
a. These are surfactants with higher ○ Stearic acid
polarity
b. These are surfactants that favor W/O *Non-ionic - forms the most stable dispersed
emulsions system because it has no charge; ideal
c. These are surfactants with lower surfactants
polarity
d. These are surfactants that favor Emulsification theories
O/W emulsions 1. Surface tension theory

*higher HLB = higher polarity, hydrophilic,

support the external phase (water)

HLB SYSTEM
Activity and HLB Value of Surfactants
2. Plastic or interfacial film theory - thin
Activity Assigned HLB film around the droplets

Antifoaming 1-3
 ○ E.g., calamine liniment
● Soft soaps

3. Oriented- wedge theory - surfactants

curved around the interface? droplets

Challenge yourself
1. A castor oil emulsion contains 30%
Challenge yourself of castor oil. How much castor oil,
Give the 3 common methods of making water, and aciaia are required to
emulsions prepare the primary emulsion in the
● Dry gum (continental) formulation of a liter of emulsion?
● Wet gum (ENGLISH)
● Forbes/Bottle Method

Methods of making emulsions

1. Continental or dry gum method
(4:2:1 O-W-G method)
● (1 acacia + 4 oil) + 2 parts
water all at once
● Volatile oils, liquid petrolatum
(mineral oil) and linseed oil
usually require a 3:2:1 or 2:2:1
ratio
2. What is HLB of a mixture of a 40%
2. English or wet gum method (no Span 60 and 60% of Tween 60?
fixed ratio) HLB of Span 60 - 4.7
● (1 granular acacia + 2 water) + HLB of Tween 60 - 14.9
4 oil in portions
ANSWER:
3. Bottle or Forbes Bottle method ● Span 60
● (1 powdered acacia+ 2 parts of 4.7 (HLB) X 40% (Composition) = 1.9
oil) +2 parts of water in portions ● Tween 60
● For volatile oils or oleaginous 14.9 (HLB) X 60% (Composition) = 8.9
substances of low viscosities. ● HLB of Mixture = 10.8
4. In-situ soap method Emulsion defects because emulsions are
● Calcium soaps - W/O thermodynamically unstable
emulsions that contain certain ● Creaming
vegetable oils, such as oleic ● Sedimentation
acid, in combination with ● Inversion
limewater (Calcium Hydroxide
solution, USP) in 1:1 ratio
 2. Aluminum Hydroxide* Gel, USP
● Uses:
● Side effects

3. Milk of Magnesia
● 7% to 8.5% magnesium hydroxide
● Chemical reaction

Aerosols
● Pressurized dosage forms that emit a
fine dispersion of liquid and/or solid
Means of detecting emulsion type materials containing one or more
1. Dilution test - addition of water/oil into active ingredients in a gaseous
the sample + visual check medium.
2. Conductivity test ● They are highly dependent on the
● O/W - Glowing electric bulb container function, valve assembly,
3. Dye solubility test - use of and propellant for drug delivery.
water-soluble or oil-soluble dye
● Water soluble (amaranth) *MDI - metered dose inhaler
● Oil soluble (Sudan red)
4. Fluorescence test - use of UV light → Advantages of aerosol dosage forms
oil has property to absorb UV light ● Dispense drug without risk of
● O/W - Continuous fluorescence contamination
● W/O - Spotty fluorescence ● Hermetic, opaque, can maintain
5. Cobaltous chloride paper test sterility
O/W - blue to pink (“blue without you”) ● Apply topically without mechanical
application evenly
Important Gel Terminologies ● Rapid volatilization of propellant gives
● Lyophobic, lyophilic, amphiphilic cooling effect
● Thixotropy - gel-sol formation ● Controlled particle size, physical form,
● Imbibition - taking up of liquid without dosage (metered valves)
measurable increase in volume
● Swelling - with increase in volume Aerosol Principles
● Syneresis - Dispersing medium is ● Product concentrate:
“squeezed out” and the gel shrinks ○ Active ingredient
● Xerogel - liquid is removed from gel ○ Antioxidants
and only the framework remains; ○ Surfactants
○ Example:gelatin sheets, ○ Solvents
tragacanth ribbons, and acacia ● Propellant
tears ○ Liquid gas/es: Nitrogen. CO2,
N2O
Examples of Gels and Magmas ○ *serves as propellant and
solvent/vehicle for product
1. Bentonite Magma, NF concentrate
● 5% bentonite, a native colloidal
hydrated aluminum silicate, in purified
water
● Thixotropic gel, suspending agent, for
alkaline pH
● Simple hydration
Aerosol assembly

1. Actuator - “press here”; with orifice

2. Stem - supports actuator and delivers
the proper form
3. Gasket - prevents leaking
4. Spring - mechanism by which actuator
retracts; holds gasket in place PARENTERALS
5. Mounting cup - holds the valve in
place; exposed to the formulation PARENTERAL
6. Housing - links dip tube and the stem ● From greek words “para” and
and actuator “enteron”
7. Dip tube - bring formulation from the ● Injectable routes if administration =
container to the valve. other than the oral
● Endotoxin are organic metabolic
Vaginal and Rectal aerosols - generally O/W products shed from G(-) bacteria,
emulsions resembling light creams; water which can cause fever and
miscible and non greasy hypotension in patients when they are
in excessive amounts in intravenous
Foam - emulsion dosage form containing (IV) injections.
dispersed gas bubbles. When dispensed, it
has a fluffy, semi solid consistency. APPLICATION OF PARENTERALS
● Rapid drug action in emergencies
● Total bioavailability
● For patient that are uncooperative,
Administration of Aerosols unconscious, unable to swallow or
● Extender devices or spacers - for tolerate oral medicine
patients who could not learn to ● Mostly administered by a HCP in a
coordinate release of the medication hospital clinic or extended health care
with inhalation. facility
Challenge yourself
What are the disadvantages of
parenterals?
● Irreversible
● Painful
● Costly
● Risky
 ● Should be sterile ● Aqueous or oily solutions or
● Should be performed by a professional suspensions can be administered in
volumes of up to 4 mL
PARENTERAL ROUTES ● Maximum of 5 mL in the gluteal region
1. INTRAVENOUS ROUTE - green and 2 mL in the deltoid of the arm
2. INTRAMUSCULAR ROUTE - yellow ● Example: Diazepam, Iron dextran
3. SUBCUTANEOUS ROUTE - blue Injection
4. INTRADERMAL - red *usually administered in the shoulder muscles,
5. INTRASPINAL buttocks, thighs
*not advisable in children’s butt but in thighs

Challenge yourself
Can you give at least 4 non-aqueous
solvents for injections?
● corn oil
● cottonseed oil
● peanut oil/ arachis oil
● sesame oil
*castor oil and olive oil can also be
considered as solvents for injections
*mineral oil and paraffin - not allowed in
Challenge yourself parenterals
Which of the following is true about parenteral
administration based on the diagram? SUBCUTANEOUS (SC or subQ) aka
A. Intramuscular is the deepest route HYPODERMIC
B. SubQ is the most parallel to the skin ● Allow slow and predictable absorption
C. Intradermal has a very long needle ● Max. amount of medication that can be
D. Intravenous has a very short needle comfortably injected is ~ 1.3mL
● Only for aqueous solutions or
INTRAVENOUS(IV OR i.v) suspensions of drugs
● Offers 100% bioavailability, rapid & ● Example: Insulin, Heparin
predictable response and high volume ○ *upper arms, abdomen, upper
administration legs
● Usually on the back of the hand or
internal flexure if the elbow Challenge yourself
● Drug solutions at high/ low pH or highly What is the technique employed to infuse
concentrated hypertonic solutions will large volumes of parenteral solutions via
damage the cells lining the vein and subcutaneous route?
cause localized pain and inflammation - Hypodermoclysis
(thrombophlebitis) → central line
INTRADERMAL (ID)
INTRAMUSCULAR (IM or i.m) ● Has slow absorption and lowest
● Is less rapid but longer lasting than IV volume of injection
● “DEPOT” ● Diagnostic determinations
● Use the Z-track method for all I.M (allergy test, tuberculin test)
injections in adults. This prevents drug desensitization, or immunization
leakage into the subcutaneous tissue, (BCG vaccine)
helps seal the drug in the muscle, and ● Only about 0.1 mL or up to 0.2mL
minimizes skin irritation ○ *anterior forearm
INTRASPINAL Cannula - hole; higher gauge = smaller hole
● Only for aqueous solutions of drugs
● Intrathecal (IT or i.t) injections are CONTAINER FOR PARENTERALS
administered into the cerebrospinal ● Transparent - for visual checking if
fluid (CSF) ~ up to 10mL there are particulates present
● Spinal anesthetic, antibiotics, ● Tightly sealed
anticancer agents (MTX, cytarabine) ● Compatible with other components
○ *between the vertebrae of the ● Withstand chosen sterilization
spine into the area of the spinal technique
column
Challenge yourself
Challenge yourself Match the following glass materials to their
Fastest onset of action type
a. Oleaginous suspension ● Highly resistant borosilicate glass -
b. Oleaginous solution Type 1
c. Aqueous suspension ● Treated soda lime glass - Type 2;
d. Aqueous solution Water attack test
*Blood contains water; aq. so it will blend with ● Soda lime glass - Type 3
your blood ● General purpose - Type 4

Often times long action is desired to reduce PARENTERAL CONTAINERS

the frequency of injections.These long-acting ● Ampoules
injections are called Respiratory or Depot ○ Type 1 glass, single use,
Preparations unpreserved, fragile
● Vials
PARTS OF SYRINGE ○ Single or multiple use
○ *Composed of rubber stopper
and aluminum
● Infusion bags
○ Collapsible bags are made of
PVC or polyolefin (less reactive
than PVC)
○ Single use
● Infusion bottles
○ Type 1 glass or semi rigid PE
plastic
○ Single use
*Flexible = no need for air inlet
*PVC = potential adsorption, leaching,
reaction
*Glass = prone to breakage
*Vials = either single or multiple
*large volume (>100) parenteral = should be
single use; no preservative (because high
preservative content is required = toxic)
*Multiple dose - must have preservative

USP Limit
SINGLE-DOSE: more than 100 mL
MULTIPLE-DOSE: 30 mL; 3 times allowable
​ to withdraw
 ○ Antioxidants
PARENTERAL SOLVENTS ■ BHT
■ BHA
WATER FOR INJECTION (WFI) ○ Chelating agents
● Pyrogen-free ○ pH adjusters & buffers
● not sterile ○ Tonicity Adjusters
● Purified ○ Suspending agents
● Without additives
STERILE WATER FOR INJECTION (SWFI) SUSPENDING AGENTS
● Pyrogen-free ● For IM and IA injectable
● NMT 0.25 USP EU/mL suspensions-cellulose derivatives
● Sterile ● polysorbates
● Without additives
BACTERIOSTATIC WFI (BWFI) Challenge yourself
● Sterile water + antimicrobial agent/s BHT and BHA are used as ___ in
● For SVPs only (NMT 5mL) parenterals
NaCl INJECTION, USP (NSS) a. Solubilizers
● 0.9% w/v b. Antimicrobial aganets
● Sterile c. Antioxidant
● Isotonic NaCl solution d. flavoring agents
● No antimicrobial agents
OTHER PARENTERAL VEHICLES COMMON EXAMPLES OF ADDITIVES
● Bacteriostatic NaCl injection - NMT
30 mL SOLUBULIZERS Cyclodextrin/CD
● Ringer’s Injection, USP- sterile (thimble-like shape)
solution of NaCl, KCl, CaCl2
● Lactated ringer’s Injection, USP -
same with Ringer + sodium lactate
(alkalizer)
● Non-aqueous solvents
○ Fixed vegetable oils
■ Corn oil
■ Cottonseed oil
■ Peanut oil
EMULSIFIERS Lecithin (egg yolk),
■ Sesame oil
sorbitan esters
■ Castor oil
■ Olive oil PRESERVATIVES Benzalkonium Cl,
○ Glycerin,PEGs PG Benzoic acid, Benzyl
○ Alcohol alcohol, chlorobutanol
○ Ethyl oleate Isopropyl myristate
(IPM) ANTIOXIDANTS Sodium metabisulfite, Vit
○ Dimethylacetamide C, Vit E, BHA, BHT

COMPONENTS OF PARENTERALS CHELATING Citric Acid, EDTA

● Active Ingredient AGENTS
● Solvent/ Vehicle + Co-solvents
○ Aqueous or Non-aqueous pH ADJUSTER HCl, H2SO4, citric acid |
● Other additives Na hydroxide/
○ Solubilizers bicarbonate/ citrate
○ Emulsifiers
○ Preservatives
 ○ Must allow desorption
BUFFER Citric Acid, Na citrate/
acetate/lactate/phosphat
*STERILIZATION - kill/destroy/remove all
e
living organisms and their spores OR their
complete removal from the preparation;
TONICITY ADJUSTERS filtration is considered as sterilization

Challenge yourself
Which method of sterilization these
belong?

● Adjusters can be NaCl, mannitol,

dextrose
● Isotonicity required for IV and ideal for
subQ, ID, IM, intrathecal and
intraocular
hypotonic - most toxic; most dangerous state;
prone to cell burst/rupture’ 1. Steam or Moist - (Autoclave)
*hypertonic - reversible

METHODS OF STERILIZATION
● STEAM OR MOIST
○ Autoclave
○ Underpressure
○ Denaturation & coagulation of
protein
○ NOT for oily prep and exposed 2. FIltration
powders
○ Most preferred (if not
specified)
● DRY HEAT
○ Oven
○ Keep things dry
○ Dehydration the slow oxidation
○ For non-aqueous prep; for
oily preparation
○ For powders
● FILTRATION
○ Millipore or sieve
○ Physical removal 3. Gas Sterilization (Ethylene Oxide gas
○ For heat-sensitive prep bag)
● GAS STERILIZATION
○ Ethylene or propylene oxide *Bacterial filtration/ filtration method -
gas Preferred method for sterilizing ophthalmic
○ Alters metabolism of cell preparations
○ For heat and moisture
sensitive prep
*Gas or chemical sterilization - Preferred ● Pass: no gel clot is formed
method for medical devices such as *Scientific name of horseshoe crab: Limulus
catheters polyphemus

Setting used MISCELLANEOUS CONCEPTS

PARENTERAL NUTRITION
● CENTRAL PN (TPN)
○ Concentrated formula which is
HYPERosmolar and must be
delivered into a central vein

● PERIPHERAL PN
○ Has similar nutrient
components as TPN but in a
LOWER concentration so it
may be delivered by peripheral
● Dry heat vein.
○ 150ºC- 170ºC
○ NLT 2 Hours ENTERAL NUTRITION
● Ionizing radiation* ● Administered orally via nasogastric
○ Using gamma rays and cathode tube via feeding gastrostomy or via
rays (20-40kGy) needle catheter jejunostomy
○ Complete and irreversible
destruction of cell components OTHER STERILE PREPARATIONS
● IRRIGATION SOLUTIONS
Validation of sterility ○ Intended to bathe or wash
1. Steam and gas sterilization - Spores wounds surgical incisions or
of Bacillus stearothermophilus body tissues
2. Dry Heat - Spores of Bacillus subtilis ● DIALYSIS SOLUTIONS
(“dry continent = SUBterrain”) ○ Used to remove toxic
3. Ionizing radiation - spores of B. substances normally excreted
pumilus, B.stearothermophilus , by the kidney
B.subtilis

A biologic indicator is a characterized

preparation of specific microorganisms
resistant to a particular sterilization process
*Rabbit test (in vivo) and LAL test (in vitro) -
method used for pyrogen testing

USP PYROGEN TESTING

● Uses rabbits
● Checks the individual rise in
temperature
● Pass: NMT 3 out of 8 showed + 0.5 C
or more/ Sum of temperature rise is
NMT 3.3 C
USP ENDOTOXIN TESTING
● Aka Bacterial Endotoxins Test USP BIOLOGICS AND BIOTECHNOLOGY
● Uses LAL (Limulus amebocyte DRUGS
lysate) from horseshoe crab
BIOLOGICS IMPORTANT TERMINOLOGIES
● Biologics, Biologicals or ● Immunization
Biopharmaceuticals ○ A process that improves the
● Medicines which contain active agents immune system
of biological origin and include ○ A process by which a person
○ Vaccines becomes protected against a
○ Enzymes disease through vaccination
○ Monoclonal antibodies (CDC definition)
○ Hematopoietic blood factors ● Vaccination
○ Cytokines ○ Use of a biologic product (a
○ Peptides vaccine) to develop active
○ Genes immunity in the patient
○ sRNA ● Toxoids
○ oligonucleotides ○ Bacterial toxins modified and
○ Carbohydrates detoxified with moderate heat
● A substance produced by a living and chemical treatment so that
source the antigenic properties remain
● Usually requires cold chain while the substance is rendered
● Critical about potency, general safety, non toxic
sterility, purity, residual moisture, ● Antigenicity
pyrogens, identity and constituent ○ Ability to specifically combine
materials with the final products of the
immune response
Biopharmaceutical class Example ○ Higher antigenicity = higher
immune response
Peptides Oxytocim
VACCINES
Proteins - ● Preparations that induce immunity
Enzymes Pancreatic lipase
Monoclonal antibodies Bevacizumab
Cytokines Inteferon beta 1b
Hormones Human Growth Hormone
Hematopoietic growth Epoeitin
factors

Vaccines Diptheria - Pertussis -

Tetanus (DPT)

Nucleic acid drugs

Genes Gendicine
Oligonucleotides Vitravine ● A vaccine may be:
siRNA No marketed products
■ Killed
Cell-based therapies Platelets ● Totally dead
Cytomegalovirus specific ● Usually needs to be re
T-cells administered over time
■ Attenuated
Carbohydrates Low molecular weight
heparin
● Alive by weakened
● Have more antigenicity
→ more permanent
What do you call the generic counterparts immunity
of proprietary biologicals?
● Biosimilar or biobetters Challenge yourself
Which of the ff vaccines is used to prevent
 cervical cancer? ○ The organism is grown in a
● Human papilloma vaccine suitable broth medium in a
● Hepatitis B vaccine controlled environment
● Dead or alive
IMPORTANT VACCINES ○ The organism may be treated
with phenol or formaldehyde or
Vaccine Protection Schedule of heat to kill it or it is genetically
From Immunization altered to keep it alive
disease ● Purification
○ The organism is separated from
BCG Tuberculosis One dose at
the broth or solvent via
(Bacillus birth up to 1
Calmette- year of age centrifugation and is suspended
Guerin) in NSS injection

DPT Diptheria, 3 doses at

Pertusis, weeks 6, 10 and GENETICALLY ENGINEERED VACCINE
Tetanus 14. 1st booster
Toxoid dose 16 to 24 ● Hepatitis B virus
months. 2nd ● surface capsid proteins that provoke
booster dose 5 an immune response
to 6 years 1. Extract DNA from virus
2. Sequence and identify target gene
OPV (oral Poliomyelitis First dose at
polio birth, 3 doses at 3. Clone the target gene into a plasmid
Vaccine) weeks vector for protein expression
6,10,14.booster 4. Transform cloned gene into yeast cells
shot , 16 to 24 5. Induce protein expression in yeats and
months
scale up protein expression
Hepatitis B Hepa B First dose within 6. Isolate and purify a large quantity of
24 hours of hepatitis B virus surface proteins
birth. Et three 7. Formulate vaccine and produce
doses at weeks hepatitis B virus vaccine
6, 10, 14

Measles- Measles First dose 9 to UPDATE on Common Covid 19 Vaccine

Lyophilized 12, second dose Pfizer mRNA 2 doses, 21
16 to 24 months days apart

TT (tetanus Tetanus First dose at Moderna 2 doses , 28

toxoids) age 10 and daes apart
second dose at
age 16 J&j/ Janssen Viral Vector 1 dose
(non
Japanese Brain fever/ First dose 9 to Replicating)
Encephalitis Swelling 12 months, Oxford- 2 doses, 21
Second dose, Aztrazeneca days apart
16 to 24 months
Sinovac/ Inactivated 2 doses, 28
Coronavac Virus days apart
How do we make traditional vaccines?
Sinopharm 2 doses, 21-28
days apart

Foremost adverse effect of concern with

immunization is hypersensitivity, most notably
● Cell culture anaphylaxis
 ● Dispensing 3. -zumab – humanized (ex.
○ Keep in original container to Omalizumab)
avoid contamination and 4. -umab – fully human ( ex.
deterioration adalumumab)
● Administration
○ Practice aseptic technique from Trivia Time!
production to administration. ● Gendicine is the first gene therapy
Most are injected, some are drug, it is an adenovirus-based DNA
taken by mouth vector that delivers cancer suppressor
● Management of symptoms gene p53 to treat head and neck
○ Analgesics may be given to cancer
manage symptoms of ● Saquinavir is the first FDA approved
immunologic response to HIV protease inhibitor
vaccines ● Exubera is the first FDA- approved
inhaled insulin but inhaled insulins
Recombinant DNA (rDNA) A.K.A hybrid were later on ignored because people
DNA preferred conventional insulin
● Produced by joining pieces of DNA ● Abraxane is the first FDA approved
from different sources leads to rapid nanoparticles drug
isolation and mass production of ○ It is a nano complex of
proteins later on led to the PACLITAXEL & ALBUMIN for
development of monoclonal antibodies the treatment of breast cancer

Trivia time! Stem cell therapy

● Humulin – first FDA approved ● Used to introduce new cells to replace
recombinant human insulin produced the damaged cells in order to repair,
in E. coli recover, and restore the normal
● Somatropin – first recombinant human function of damaged or diseases
growth hormone (hGH) tissues or organs.

Do you know that the hirudin produced by Human Genome Project

the leech Hirudo medicinalis is used to ● An international, collaborative research
prevent clotting during surgeries program whose goal was the
● Lepirudin – a recombinant hirudin complete mapping and
derived from yeast cells – is a highly understanding of all the genes of
specific direct inhibitor of thrombin human beings.

Monoclonal antibodies (mAb) —--- END OF BIOLOGICS —--

● Fusing two cells to produce a
hybridoma NOVEL DOSAGE FORMS AND DRUG
○ The produced Ab is called mAb DELIVERY SYSTEMS
● Muromonab (OKT3) is the first FDA
approved monoclonal antibody drug TOPICAL AND TRANSDERMAL
○ Murine Topical Administration
○ Antibody against T- lymphocyte ● Iontophoresis
CD3 ○ An electrochemical method that
○ Reverses acute kidney enhances drug transport by
transplant rejection creating a potential gradient
Types of monoclonal antibodies through the skin.
1. -omab - murine (ex.Muromomab)
2. -ximab – chimeric (ex. Infliximab) ● Phonophoresis
 ○ transport of drugs through the d. Thickness of horny layer (thicker
skin using ultrasound layer = decreased absorption)
e. None of the choices

Transdermal Patch

Principle of Iontophoresis

Part Characteristic Example

Backing layer Occlusive to retain - Polypropylene

skin moisture and - Polyethylene
hydrate the site of - Polyolefin
application

Adhesive layer Pressure sensitive Polybutyl

nonirritating allow acrylate
easy peel-off

Drug release Polyethylene

membrane

● Tape
○ Consists of the drug(s) A. Backing - protect the system from
impregnated into a durable yet environmental entry and from loss of
flexible woven fabric or drug from the system or moisture from
extruded synthetic material that the skin
is coated with an adhesive B. Drug reservoir - store and release the
agent. drug at the skin site
C. Protective Peel strip - Removed
Transdermal administration before application and enables drug
release
D. Adhesive layer - maintain contact with
the skin after application
E. Control Membrane - control precisely
and predictably the release of
medicine.

Challenge yourself
Which of the following inversely affect
percutaneous absorption?
a. Drug concentration (inc. conc = inc.
absoprtion)
b. Area of application (inc. area = inc.
absorption)
c. Hydration of the skin (more hydrated =
inc. absorption)
 d. Advair diskus
ORAL ADMINISTRATION
● Oral Thin Film (OTF) VAGINAL ADMINISTRATION
○ thin, flexible sheet of material ● Intrauterine device (IUD)
usually composed of a polymer ○ Used for contraception; the
material; in a rapid dissolving drug is contained in the
form polymeric matrix and is
○ adsorbed directly into a released upon contact with the
systemic circulation. vaginal fluids.
● Mucoadhesive system ● Vaginal ring
○ designed to adhere to the gum ○ A biometrial which contains the
or inner cheek to provide a drug in the core of the ring
controlled and sustained where ir is released
release of drug (e.g immediately and continuously
Testosterone) through the
buccal mucosa.

OTHERS
● Autoinjection systems
○ (E.g. epinephrine injection for
IM use)
○ Emergency supportive therapy
of allergic reactions
(anaphylaxis)
● Wafer implants
○ Sterile wafers that usually
contain biodegradable
● Medicated gums polymers with the drug
○ Semisolid confection that is embedded.
designed to be chewed, ● Nanoparticles
releasing the API into the saliva ○ Solid colloidal particles that
● Osmotic pump include both nanospheres and
○ Rate-controlled release nanocapsules with a capacity to
release drugs.

Challenge Yourself
Which of the following aids in smoking RADIOPHARMACEUTICALS: only the
cessation? essentials
a. Nicorette Usually for diagnostic imaging
b. Hydromorphine Oros Board exam items:
c. Nitro-Dur ● 131I - thyroid function
 ● 131I-orthoiodohippurate - kidney 153Samarum for relief of pain in patients
function (aka renogram) lexidronam with confirmed
● 201Tl-thallous chloride - myocardial osteoblastic metastatic bone
perfusion imaging (MPI) lesions
● 99mTc - “gold standard’ for MPI
89Strontium chloride Indicated for the relief of bone
Some have therapeutic uses designed to pain in patients with
deliber therapeutic doses of ionizing radiation painful skeletal metastases
to specific disease sites, such as cancerous
tumors, with high specificity in the body.
99m Technetium Generally for in vivo
diagnostic imaging; most
● Thyroid disease - treated with used*
sodium iodide, 131I.
● Polycythemia vera - treated with 201Thallium chloride Myocardial perfusion imaging
sodium phosphate, 32P
113Xenon gas Evaluation pf pulmonary
function, lung imaging,
Radiopharmaceutical therapy (RPT) assessment of cerebral blood
involves the targeted delivery of radiation to flow
tumor cells or to the tumor microenvironment.
90Yttrium chloride Radiolabeling
SUMMARY OF FDA-approved 90Yttrium ibritumomab Chemotherapeutic against
Radiopharmaceuticals tiuxetan lymphomas
Name Detects or use *has several drug forms
14C urea Gastric urease to diagnose H. Medical Devices
pylori
According to FDA Circular 2020-001, the following is the
67Gallium citrate Hodgkin's Disease,
lymphoma, and bronchogenic classification of medical devices based on risk level:
carcinoma, inflammatory
lesions. Class A - Low (example: cotton)
Class B - Low to Moderate (example: contact lens)
11Indium For in vivo diagnostic imaging Class C - Moderate to High (example: condom, pero
or radiolabeling class D ang may spermicide and ang natural membrane
ambot kung ano na sya wala pako katry haha)
123, 125, 131 Iodine Several, depends on the form Class D - High (example: Annuloplasty ring aka mitral
(e.g. 123) evaluates thyroid valve ring which helps close the valve as tightly as it
function) should)
Refer to FDA Circular 2020-001 for the classification per
medi
177Lutetium dotatate Treats somatostatin
receptor-positive
gastroenteropancreatic
neuroendocrine tumors

99Molybdenum or 99m Thyroid, Urinary bladder,

Technetium nasolacrimal imaging

223Radium dichloride Treats castration-resistant

prostate cancer,
symptomatic bone
metastases and no known
visceral
metastatic disease