Presented by

Dr. Rajesh Kadam

JUNIOR RESIDENT
Dept of Pharmacology
MGM’s Medical college, Aurangabad (ms)
Major route of drug administration are:
A) Topical
A) Skin
B) Conjunctival

A) Enteral
A) Oral
B) Sublingual or Buccal
C) Rectal
D) Inhalational
E) Nasal
A) Parenteral
A) Subcutaneous
B) Intramuscular
C) Intravenous
D) Intradermal injection
 Provide increased local concentration of the drug.

 Improve the compliance of the patient.

 Make drug utilization more convenient.

 Reduces toxic effects of the drug.

 Delivery of drug by conventional route.

 Reduces side effects.

 Enhances target specificity.

 Increases drug bioavailability in required zone

1) Oral control release drug formulations
2) Nasal drug delivery system
3) Pulmonary drug delivery system
4) Transdermal drug delivery system
5) Others
 All Other Transdermal
2% 8%
Implant
10%

Oral CR
60%

Inhalation
27%
Controlled drug delivery is one which delivers the drug at a predetermined rate,
for locally or systemically, for a specified period of time.
 Control drug release has been achieved by following classes of control drug
delivery system:
1) Dissolution
1) Matrix
2) Encapsulation

1) Diffusion
1) Matrix
2) Reservoir

1) Combination of both Dissolution & Diffusion

2) Osmotic pressure control system

 These systems are most commonly employed for production of enteric coated
dosage forms.

 To protect the stomach from the effects of drug such as aspirin, a coating that
dissolves in alkalline media is used.

 This inhibits release of drug from the device unless it reaches the higher ph of the
intestine.
 Also called as Monolith dissolution controlled system.

 It can be either a drug impegnated shere or tablet which will be subjected to slow
erosion
 Dissolution is Controlled by:
1.Altering porosity of tablet.

2.Dissolving at slower rate.

 Drug release determined by dissolution rate of polymer.

 Examples: Dimetane extencaps.

 Soluble drug

Slowly dissolving
matrix
 Also Called as Coating dissolution controlled system.

 Drug is coated with a given thickness coating, which is slowly dissolved in the
contents of gastrointestinal tract.
 An alternative method is to administer the drug as group of beads that have
coating of different thickness.
 Since the beads have different coating thickness, their release occurs in a
progressive manner.
Soluble drug

Slowly dissolving
or erodible coat
 Diffusion process shows the movement of drug molecules from a region of
higher concentration to one of lower concentration across the membrane.

 Commonly when a water insoluble membrane encloses a core of drug, it must

diffuse through the membrane.
 Also called as Laminated matrix device.

 In the system, a water insoluble polymeric material encases a core of drug. Drug
will partition into the membrane and exchange with the fluid surrounding the
particle or tablet.
 Additional drug will enter the polymer, diffuse to the periphery and exchange
with the surrounding media.

 Drug core surrounded by polymer membrane which controls release rate.

 Rate controlling mechanism - partitioning into membrane with subsequent
release into surrounding fluid by diffusion.

 Commonly used polymers - HPC, ethyl cellulose & polyvinyl acetate.

 Examples: Nico-400, Nitro-Bid

Advantages:
 Zero order delivery is possible
 Release rate is variable with polymer type

Diadvantages:
 Difficult to deliver high molecular weight compound
 Potential toxicity if system fails
 Increased cost as per dosage
Rate controlling steps :
Polymeric content in coating, thickness of coating, hardness of
microcapsule.
 A solid drug is dispersed in an insoluble matrix and the rate of release of drug is
dependant on the rate of drug diffusion.

 Homogenous dispersion of solid drug in a polymer mixture.

Advantages:
 Easier to produce than reservoir or encapsulated devices
 High molecular weight compound can be deliver

Disadvantages:
 It cannot provide zero order release
Rate controlling step:
Diffusion of dissolved drug in matrix.
 A semi permeable membrane is placed around a tablet, particle or drug solution
that allows transport of water into the tablet with eventual pumping of drug
solution out of the tablet through a small delivery aperture in tablet coating.

 Two types of osmotically sustained systems are:-

 Type A contains an osmotic core with drug

 Type B contains the drug in flexible bag with osmotic core surrounding.
 A new system is acquired i.e. GRDDS to increase the time available for drug
absorption.

 Gastro retentive systems can remain in the gastric region for several hours and
hence significantly prolong the gastric residence time of drugs.
 In this technique the gastro retention is achieved by floatation of the dosage form
in gastric fluid.

 Floating drug delivery system have a bulk density less than gastric fluid & so
remain buoyant in the stomach without affecting gastric emptying rate.
 The following approaches have been used for the design of floating dosage forms
of single- and multiple-unit systems.

Single-Unit Dosage Forms:

 In Low-density approach the globular shells apparently having lower density

than that of gastric fluid can be used as a carrier for drug for its controlled
release.
 Multiple-Unit Dosage Forms:

 The purpose of designing multiple-unit dosage form is to develop a reliable

formulation.

 Micro spheres have high loading capacity and many polymers have been used
such as albumin, gelatin, starch & polymethacrylate.

 Spherical polymeric micro sponges, also referred to as “micro balloons,” have

been prepared.

 Micro spheres have a characteristic internal hollow structure and show an

excellent in vitro floatability.
 Effervescent Floating Dosage Forms:

 These are matrix types of systems prepared with the help of swellable polymers
such as methylcellulose and chitosan and various effervescent compounds, e.g.,
sodium bicarbonate, tartaric acid, and citric acid.

 They are formulated in such a way that when in contact with the acidic gastric
contents, CO2 is liberated and gets entrapped in swollen hydrocolloids, which
provides buoyancy to the dosage forms.
 Non-effervescent floating dosage forms use a gel forming or swell able cellulose
type of hydrocolloids, polysaccharides, and matrix-forming polymers like
polycarbonate, polyacrylate..

 The formulation method includes a simple approach of thoroughly mixing the

drug and the gel-forming hydrocolloid.
 After oral administration this dosage form swells in contact with gastric fluids
and attains a bulk density

 The air entrapped within the swollen matrix imparts buoyancy to the dosage
form.

 The so formed swollen gel-like structure acts as a reservoir and allows sustained
release of drug through the gelatinous mass
 Pulsatile drug delivery system is defined as the rapid and transient release of
certain amount of drug molecules within a short time period immediately after a
predetermined off-release period, i.e., lag time.

 Pulsatile drug delivery aims to release drug on programmed pattern i.e. at

appropriate time and at appropriate site of action.

 Example:
 Pulsincap
Advantages

 Extended daytime or night-time activity

 Reduced side effects
 Reduced dosage frequency
 Reduction in dose size
 Improved patient compliance
 Lower daily cost to patient due to fewer dosage units are required by the
patient in therapy.
 Drug adapts to suit circadian rhythms of body functions or diseases.
 Drug targeting to specific site like colon.
 Protection of mucosa from irritating drugs.
 Drug loss is prevented by extensive first pass metabolism
 The Pulsincap system is an example of such a system that is made up of a water
insoluble capsule body filled with drug formulation.

 The body is closed at the open end with a swellable hydrogel plug.

 The length of plug decides lag time.

 The plug material consists of insoluble but permeable and swellable polymers
(eg, polymethacrylates)
Definition:

Transdermal drug delivery system can deliver the drugs through the skin
portal to systemic circulation at a predetermined rate and maintain clinically
the effective concentrations over a prolonged period of time.
 These are painless, non adhesive way to deliver drug directly into body.

 They are useful where drugs that are breakdown by the stomach acid,
extensively degraded by liver.
 Useful in controlled, steady delivery of medication over long period of time .
 They have very few side effects as compared to oral route.

 These are easy to use and to remember.

 It can be used as an alternative to people who cannot take medication orally.

 Patient compliance.

 They are cost effective.

 TDDS cannot achieve high drug levels in blood / plasma.

 We cannot give drugs of large molecular size.

 TDDS cannot deliver in pulsatile manner.

 It cannot given if drug or formulation causes irritation to skin.

 Adhesive may not adhere well to all types of skin.

 Uncomfortable to wear.

 May not be economical.

 Single-layer Drug-in-Adhesive

 Multi-layer Drug-in-Adhesive

 Reservoir

 Matrix

 Vapour patch
 The adhesive layer of this system also contains the drug.

 In this type of patch the adhesive layer not only serves to adhere the various
layers together, along with the entire system to the skin, but is also
responsible for the releasing of the drug.

 The adhesive layer is surrounded by a temporary liner and a backing.

 The multi-layer system is different however that it adds another layer of drug-in-
adhesive, usually separated by a membrane.
 Unlike the Single-layer and Multi-layer Drug-inadhesive systems the reservoir
transdermal system has a separate drug layer.

 The drug layer is a liquid compartment containing a drug solution or suspension

separated by the adhesive layer.

 In this type of system the rate of release is zero order.

 The Matrix system has a drug layer of a semisolid matrix containing a drug
solution or suspension.

 The adhesive layer in this patch surrounds the drug layer partially overlaying it.
 In this type of patch the adhesive layer not only serves to adhere the various
layers together but also to release vapour.

 They release essential oils for up to 6 hours and are used in cases of decongestion
mainly.
 Intranasal drug delivery is now recognized to be a useful and reliable alternative
to oral and parenteral routes.

 Recently, the nasal mucosa has seriously emerged as a therapeutically viable

route for the systemic drug delivery.
 Hepatic first pass metabolism avoided.

 Rapid drug absorption and quick onset of action.

 Bioavailability of larger drug molecules can be improved by means of absorption

enhancer.

 Convenient for long term therapy, compared to parenteral medication.

 Easy and convenient.

 Easily administered to unconscious patients.

 Pathologic conditions such as cold or allergies may alter significantly the nasal
bioavailabilty.

 Relatively inconvenient to patients possibility due to nasal irritation.

 Nasal cavity provides smaller absorption surface area when compared to GIT.
 Nasal gels

 Nasal Drops

 Nasal sprays

 Nasal Powder

 Liposome

 Microspheres
 The respiratory tract is one of the oldest routes used for the administration of
drugs.

 Over the past decades inhalation therapy has established itself as a valuable tool
in the local therapy of pulmonary diseases such as asthma or COPD (Chronic
Obstructive Pulmonary Disease) .
 It is needle free drug delivery system.

 It requires low and fraction of oral dose.

 Pulmonary drug delivery having very negligible side effects since rest of body is
not exposed to drug.

 Onset of action is very quick with pulmonary drug delivery.

 Degradation of drug by liver is avoided in pulmonary drug delivery.

 Targeting specificity.

 Drug irritation and toxicity.

 Immunogenicity of proteins

 Drug retention and clearance.

 Aerosol preparations are stable dispersions or suspensions of solid material and
liquid droplets in a gaseous medium.

 The drugs, delivery by aerosols is deposited in the airways by:

 Gravitational sedimentation
 Inertial impaction
 Diffusion

 Mostly larger drug particles are deposited by first two mechanisms in the
airways, while the smaller particles get their way into the peripheral region of the
lungs by following diffusion.
 There are three commonly used clinical aerosols:
 Nebulizers
 Metered–dose Inhaler (MDI)
 Dry-powder inhaler (DPI)

 The basic function of these three completely different devices is to generate a

drug-containing aerosol cloud that contains the highest possible fraction of
particles in the desired size range.
 Nebulizers are widely used as aerosolize drug solutions or suspensions for drug
delivery to the respiratory tract and are particularly useful for the treatment of
hospitalized patients.

 Delivered the drug in the form of mist.

 There are two basic types:

 Air jet
 Ultrasonic nebulizer
Jet nebulizers Ultrasonic nebulizers
 DPIs are bolus drug delivery devices that contain solid drug in a dry powder mix
(DPI) that is fluidized when the patient inhales.

 Dry powder formulations either contain the active drug alone or have a carrier
powder (e.g. lactose) mixed with the drug to increase flow properties of drug.

 DPIs are a widely accepted inhaled delivery dosage form, particularly in Europe,
where they are currently used by approximately 40% of asthma patients.
 Propellant-free.

 Less need for patient co-ordination.

 Less formulation problems.

 Dry powders are at a lower energy state, which reduces the rate of chemical
degradation.
 Dependency on patient’s inspiratory flow rate and profile.

 More expensive than pressurized metered dose inhalers.

 Not available worldwide.

 Used for treatment of respiratory diseases such as asthma and COPD.

 They can be given in the form of suspension or solution.

 Particle size of less than 5 microns.

 Used to minimize the number of administrations errors.

 ,

 It can be deliver measure amount of medicament

accurately.
 It delivers specified amount of dose.

 Small size and convenience.

 Usually inexpensive as compare to dry powder inhalers and nebulizers.

 Quick to use.

 Multi dose capability more than 100 doses available.

 Difficult to deliver high doses.

 There is no information about the number of doses left in the MDI.

 Accurate co-ordination between actuation of a dose and inhalation is essential.

 MARKETED DRUGS Dry Powder Inhaler
Active Ingredient Brand Manufacturer Country

Terbutaline 0.25mg Bricanyl AstraZeneca UK

Beclometasone Becloforte Cipla Limited India
dipropionate 250mcg

Fluticasone propionate Flixotide GlaxoSmith United

Kline Kingom
Salbutamol Salbutamol Dry Cipla Limited India
Powder Capsules

Ipratropium Bromide ATEM Chiesi Farmaceutici Italy

20 mcg

Xinafoate Seretide Evohaler GlaxoSmithKline UK

22-Apr-12
74
 Metered Dose Inhalers (MDI)
Active Ingredient Brand Manufacturer Country

Salbutamol pressurised Asthalin Cipla India

inhalation (100µg)

albuterol Ventolin GlaxoSmithKline India

levalbuterol HCl Xopenex 3M Pharnaceuticals U.S.A.

Fluticasone50 μg Flixotide GlaxoSmithKline New Zealand

Formoterol Fumarate12 Ultratech India

mcg
22-Apr-12
75
Traditional insulin drug delivery system:

Insulin therapy via subcutaneous or other parenteral route in diabetic patient is

preferred but on continuous administration there may be chance of
 peripheral hyperinsulinemia,
 formation of thrombus, inflammation &
 irritation at the site.
 Also patient suffering from needle phobia hesitate to take it.
 Needle free insulin injection provides following advantages:
 Improve concordance with insulin regiment.

 Improve the patient health/well-being.

 Eliminates the need for sharp disposal and avoids needle stick injuries.

 Emotional benefits of using a needle free devices.

 No sharp to dispose off.

 Fast injection, insulin is delivered in less than 0.3 seconds, regardless of dose.
 No additional pressure required to delivered large doses.
 Jet injectors:
A jet injector is a type of medical injecting syringe that uses a high-pressure
narrow jet of the injection liquid instead of a hypodermic needle to penetrate the
epidermis.

It is powered by compressed air or gas, either by a pressure hose from a large

cylinder, or from a built-in gas cartridge or small cylinder.
 Inhalable insulin:

Inhalable insulin (Fig: 3) was available from September 2006 to October 2007 in
the United States as a new method of delivering insulin, a drug used in the
treatment of diabetes.
 Insulin spray:

 The buccal route is another promising alternative for insulin delivery.

 The buccal area having an abundant blood supply, it offers some advantages such as
a means to deliver the acid labile insulin, and elimination of insulin destruction by
first pass metabolism.
 Insulin Pen:
There are two pen systems:

1. A replaceable cartridge pen reuses the pen portion. When the insulin is empty,
the vial is replaced by inserting a new one.

2. A prefilled pen is entirely disposable. When the insulin is gone, the entire unit
is discarded.
 Advantages:

 More convenient and easier to transport than traditional vial and syringe.

 Repeatedly more accurate dosages.

 Easier to use for those with visual or fine motor skills impairments.

 Less injection pain

 Disadvantages:

 Unlike the traditional syringe, pens are usually restricted to full or half unit
dosing.
 You are also not able to mix two different insulins in the same pen.
 In addition, insurance coverage for insulin pens in the United States may vary
widely.
 Insulin micropump
 Insulin port
 Transdermal patches
(a) Transdermal Delivery Systems :
 Nesterone is a newer progestin. When used as a cream to the skin it provides
effective contraception.
 Combined contraceptive transdermal patches are also found very
effective.
 Patches are used like pills – 3 weeks on and 1 week off.
(b) Uniplant :
 single rod implant, containing 38 mg of nomegesterol (newer progestin) with a
release rate of 100 μg/day.
 It provides contraception for 1 year.
(c) Biodegradable Implants :
 Available by the name of capronor, releases levonorgesterol from polymer 6-
cap-rolactone.

(d) Injectable Contraceptives:

 In the form of microspheres using copolymer (lactide-glycolide) have been
studied.

 Hormone currently used in the microsphere (0.06- 0.1 mm diameter) is

either norethindrone or norethindrone combined with ethinyl estradiol.
 Injection is given over the gluteal muscle.
(e) Vaginal Rings :
These contain levonorgestrel covered by a sialistic tubing. These are
5-6 cm in diameter. These can be replaced every 90 days.

(f) Combined Ring :

These are soft & transparent ethylene vinyl rings. These have ethinyl
estradiol & etonogestrel. The ring is 5 cm in diameter.

(g) Quinacrine pellets:

These are inserted into the uterine cavity transcervically with the help of
hysteroscope.
THANK YOU