15/08/2020

OUR LADY OF FATIMA UNIVERSITY

UNIT OUTCOMES
College of Pharmacy
 At the end of this module, the students are
expected to:
BIOPHARMACEUTICS & 1. Introduce Biopharmaceutics & Pharmacokinetics
2. Define LADMER system
PHARMACOKINETICS 3. Describe the pharmacotechnical
parameters affecting liberation and discuss its
PHBP 311
clinical significance

Introduction to
Biopharmaceutics
WEEK 2

UNIT OUTLINE CHECKLIST

1. Define important terms  Read course outcomes

2. Discuss importance of measuring drug  Read course guide prior to class
concentration attendance
3. Discuss Physicochemical properties  Proactively participate in discussions
4. Define rate limiting step  Watch videos related to the topic
 Participate in discussion board
(Canvas)
 Answer and submit course unit tasks

REQUIRED READINGS/VIDEOS

 Please watch the following videos thru the given link.

 https://www.youtube.com/watch?v=uOcpsXMJcJk
 https://www.youtube.com/watch?v=Jiml3iGBs88

 NOTE: This has been assigned to you by your instructor

during the previous meeting.

Week 1

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BIOPHARMACEUTICS Bioavailability

The science that examines the A measurement of the rate and extent
interrelationship of the physicochemical
properties of the drug, the dosage form in of systemic absorption of
which the drug is given, and the route of therapeutically active drug
administration on the rate and extent of
systemic drug absorption.
The study of the chemical and physical
properties of drugs, their components, and
their activities in living organisms.

Pharmacokinetics L LIBERATION
A ABSORPTION
 The study of the time course of drug
movement in the body during
D DISTRIBUTION
absorption, distribution, and
elimination.
M METABOLISM
E EXCRETION
R RESPONSE

Clinical
Pharmacokinetics
 Applicationof pharmacokinetic
A A A methods to drug therapy.
D D D  the study of the relationships
M E between drug dosage regimens
E and concentration–time profiles

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Clinical Pharmacokinetics Population Pharmacokinetics

 Study of pharmacokinetics differences of drugs in

various population
Three fundamental parameters
 TDM ( Therapeutic Drug Monitoring)
 Clearance
 volume of fluid completely cleared of drug per  Employed for very potent drug to optimize efficacy and to
prevent any adverse toxicity
unit time
 Volume of distribution  CPKS ( Clinical Pharmacokinetic Service)
 apparent volume into which the drug has  Provides pharmacokinetic and drug analysis services for safe
distributed to produce the measured drug monitoring
concentration
 Elimination half life
 time taken for 50% of the drug to be eliminated

Experimental Pharmacokinetics
Therapeutic range
Drug
mg/L
Digoxin 0.5 - 2.1  Development of biologic sampling techniques,
analytical methods for the measurement of
Amiodarone 1.0 - 2.5 drugs and metabolites and procedure that
Salicylate 150 - 300 facilitates data collection and manipulation
Theophylline 10 - 20
Phenytoin 10 - 20
Carbamazepine 5.0 - 12

Theoretical Pharmacokinetics PHARMACOKINETICS

 Development of pharmacokinetics models  Model – a hypothesis using
that predict drug disposition after mathematical terms to describe
administration quantitative relationship concisely.
 Invivo- involves human subjects/ laboratory  Empirical
animals  Physiological
 Invitro – employs test apparatus and equipment  Compartmentally based
without involving human subjects/ laboratory
animals

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Pharmacokinetic Models Pharmacodynamics

 Catenary
 The study of the relation of the
 Mammillary
drug concentration or amount at
 Physiologic
Pharmacokinetic the site of action and its
pharmacologic response.

Clinical Toxicology Measurement of Drug Concentrations

 Sampling of biologic specimen
 Invasive Method
 The study of the adverse effects of  Requires surgical/ parenteral intervention
 Sampling of blood, spinal fluid, synovial fluid,
drugs and toxic substances in the
tissue biopsy
body
 Non- invasive method
 Without surgical/ parenteral intervention
 Feces, Urine, saliva

Importance of measuring
plasma drug concentration
 Adjustment of the drug dosage in order to
 Blood individualize and optimize therapeutic drug regimen
 Highly specialized tissue composed of many  Provides guide to the progress of disease state
different kinds of components  Enable to modify the drug dosage accordingly
 Whole blood  clot  centrifuge  supernatant  SERUM
 Whole blood  (+) heparin  centrifuge  supernatant 
PLASMA

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 MEC (Minimum effective concentration)

 Needed to produce the desired pharmacologic
effect
 MTC (Minimum Toxic concentration)
 Needed to just barely produce toxic effects
 Onset of time
 Time required to reach MEC
 Peak time
 time of Maximum drug conc in the plasma and a
rough marker of average rate of drug absorption

Relationship between the drug,

 Peak Concentration
the drug product, and the
 Maximum drug concentration
pharmacologic effect
 Duration of Drug action
 Difference between the onset of time and time for
the drug to decline back to MEC
 AUC (Area Under the Curve)
 Amount of drug absorbed systematically
 Total area found under the plasma concentration vs
time curve from the initial dose to final elimination
of the drug from the body

Biopharmaceutic Considerations in
Drug Product Design
Involves factors that influence:
a. Design of drug product  Therapeutic objective
b. Stability of drug within the drug  Drug (API)
product  Route of administration
c. Release of the drug from the drug
 Drug dosage and dosage regimen
product
 Type of drug product
d. Rate of dissolution/ release of the drug
from at the absorption site  Excipients

e. Delivery of drug to the site of action  Method of manufacture

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Drug Disposition Drug Exposure and Drug

Response

The description of  Drug exposure refers to the dose and

drug distribution and various measure of acute or integrated
drug concentrations in plasma and
elimination. other biological fluid.
 Drug response refers to the direct
measure of the pharmacologic effect
of the drug

Design of the appropriate Physicochemical Properties

dosage form or delivery
system depends on A. Drug Dissolution

 Physical and chemical properties of the drug B. Drug Solubility

 Dose of the drug C. Particle Size and Surface Area
 Route of administration D. Partition Coefficient and Extent of Ionization
 Type of Drug system desired E. Salt Formation
 Desired therapeutic effect
F. Polymorphism
 Physiologic release of the drug from the delivery
system G. Chirality
 Bioavailability of the drug at the absorption site H. Hydrates
 Pharmacokinetics and pharmacodynamics of the I. Complex Formation
drug

Physicochemical Properties Physicochemical Properties

 A. Drug Dissolution B. Drug Solubility

the rate at which the solid drug enters in a saturated solution is a static
into solution is often the rate limiting (equilibrium) property. The
step in bioavailabilty. dissolution rate of a drug is a dynamic
property related to the rate of
absorption.
The Noyes-Whitney equation
describes the diffusion controlled rate
of drug dissolution

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Physicochemical Properties Physicochemical Properties

 C. Particle Size and Surface Area  D. Partition Coefficient

inversely related  The partition coefficient of a drug is
the ratio of the solubility of the drug,
As solid drug particle size decreases, at equilibrium, in a non-aqueous
particle surface area increases. solvent

 Inc in the no of carbon

↓PS  ↑ SA  Decrease water solubility WATER
OCTANOL

Physicochemical Properties Physicochemical Properties

 Extent of Ionization  D. Partition Coefficient and Extent of

 Drugs that are weak electrolytes (acids or Ionization
bases) exist in both an ionized form and a
nonionized form in solution.  The Henderson-Hasselbalch equation
 The extent of ionization depends on the pKa
describes the relation between the ionized
of the weak electrolyte and the pH of the and the nonionized forms of a drug as a
solution. function of pH and pKa
POLAR and
 The ionized form is ____________,
therefore more _____________,
Water soluble than the 50% ionized
nonionized form pH = pKa  50% unionized

Physicochemical Properties Physicochemical Properties

 E. Salt Formation Salt Formation

 The choice of salt form for a drug depends on the WEAKLY BASIC DRUGS
desired physical , chemical , or pharmacologic Hydrochloride
proper ties. Sulfate
WEAKLY ACIDIC DRUGS
potassium and sodium Citrate
• provide slower
• greater stability salts gluconate salts
dissolution
• less local irritation at the estolate, napsylate,
• slower bioavailability
absorption site and stearate salts
• longer duration of
• less systemic toxicity
action  chloramphenicol

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Physicochemical Properties Physicochemical Properties

F. Polymorphism
 the ability of a drug to exist in more than G. Chirality
one crystalline form
 the ability of a drug to exist as optically active
 Amorphous, or noncrystalline, forms of a stereoisomers or enantiomers
drug have faster dissolution rates than do  Individual
enantiomers may not have the same
crystalline forms. pharmacokinetic and pharmacodynamic activity.
 Forexample, ibuprofen exists as the R- and S-
Same DIFFERENT
PHYSICAL enantiomers; only the S-enantiomer is
CHEMICAL
pharmacologically active.
STRUCTURE PROPERTIES

Physicochemical Properties

H. Hydrates
 Drugs may exist in a hydrated, or solvated, form or
as an anhydrous molecule
 Dissolution rates differ for hydrated and anhydrous
forms.

Physicochemical Properties Physicochemical Properties

 Complex Formation
Complex Formation  Complex formation usually alters the
A complex is a species formed by the reversible physical and chemical characteristics of the
or irreversible association of two or more drug.
interacting molecules or ions.  Large drug complexes, such as drug-protein
 Chelates are complexes that typically involve a complexes, do not cross cell membranes
ring-like structure formed by the interaction easily.
between a partial ring of atoms and a metal  For example:
Ex. hemoglobin, insulin, cyanocobalamin The chelate of tetracycline with calcium is
less water soluble and is poorly absorbed.

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LADMER
SYSTEM
L ADMER

Liberation

Liberation Liberation
delivery of the active the first step which determines onset of
action, rate of absorption, availability,
ingredient from a dosage etc., which is true for all drug products
form into solution. by all routes of administration (except
intravenous and the peroral use of true
solutions)
controlled by the characteristics of the drug
product.

Liberation

 state in which any residue of the

Disintegration
tablet, except fragments of
Dissolution insoluble coating, remaining on the
screen of the test apparatus in the
soft mass have no palpable firm
core.

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Rate Limiting Step

the process by which a

the process with the slowest
chemical or drug becomes
dissolved in a solvent. rate constant in a system of
simultaneous kinetic
processes.

ASSIGNMENT

 Reminder: Prepare for Online Quiz.

 Note: Submit this thru CANVAS

END OF DISCUSSION

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