BIOPHARMACEUTICS

&
PHARMACOKINETICS

INTRODUCTION
• Bio – life

• Pharmaceutics
– general area of study concerned with
the formulation, manufacture, stability

and effectiveness of pharmaceutical

dosage forms.
 Biopharmaceutics
• study of the factors
influencing the
bioavailability of a drug
in man and animals and
the use of this
information to optimize
pharmacological or
therapeutic activity of
drug products in clinical
application.
 Biopharmaceutics

• study of the influence of formulation on

therapeutic activity of a drug product.
 Biopharmaceutics

• study embracing this relationship between the

physical, chemical and biological sciences as
they apply to drugs, dosage forms, and to drug
action.
 Biopharmaceutics

• Modern biopharmaceutics is the study of the

relationship of the physico-chemical properties
and in vitro behavior of the drug and drug
product on the delivery of the drug to the body
under normal or pathologic conditions.
 Drug
• agent intended for use in the diagnosis,
mitigation, treatment, cure or prevention of
disease in man or in other animals.
• It may be:
1. synthetic 4.
biological
2. semi-synthetic 5. natural
3. chemical
 Drug
• Modern drugs are potent chemical substances
that must be fabricated into a drug product
before use.
• Generally, the drug is combined with other
ingredients into a drug formulation, which
may be a solution, tablet, capsule or
suppository.
 Rationale
• The development of biopharmaceutic
principles allowed for the rational design of
drug products, which would enhance the
delivery of active drug, and optimize the
therapeutic efficacy of the drug in the patient.
 Drug Product
• a finished dosage form that contains an active
drug ingredient generally, but not necessarily,
in association with inactive ingredient.
• formulation or matrix in which the drug is
contained
• The term may also include a dosage form that
does not contain an active ingredient intended
to be used as placebo.
Drug Action

 result of an interaction between the drug

substance and functionally important cell
receptors or enzyme systems.
 This response is due to the alteration in
the biologic processes that were present
prior to the drug administration.
 In vitro – glass / outside
 referring to a process or reaction carried
out in a culture dish or test tube
 In vivo – in the living organism
Effects of Biopharmaceutics
 Generic equivalency
 Drug availability
 Therapeutic efficacy
 Drug substitution
Effects of Biopharmaceutics
 Drug product selection  .
*drug product should be
cost-effective

*drug product selection

should be according to
the patient’s capability

*drug product selection

should be based upon
the patient’s diagnosis
Aim

 The aim of biopharmaceutics is to adjust

the delivery of drug to the general
circulation in such a manner as to provide
optimal therapeutic activity for the patient.
Aim

 Biopharmaceutic studies allow drugs to

be formulated rationally based on
pharmaceutic properties.
Some Pharmaceutic Properties

 Some drugs are intended for topical or

local therapeutic action at the site of
administration. For these drugs,
systemic absorption is undesirable.
Some Pharmaceutic Properties

 Drugs intended for local activity generally

have a direct pharmacodynamic action
without affecting other body organs.
These drugs may be applied topically to
the skin, nose, eyes, mucous membranes,
buccal cavity, throat and rectum.
Factors Affecting Biopharmaceutics

 a. Physical state of the drug:

- according to the 4 states of matter

 The crystal or amorphous forms and/or

the particle size of a powdered drug
have been shown to affect the
dissolution rate, and thus the rate of
absorption, for a number of drugs.
Factors Affecting Biopharmaceutics

.
 By selective control
of the physical
parameters of a
drug, biologic
response may be
optimized.
b. dosage form
- delivery system by which the drug could
be made available or administered.
b. dosage form

Each of dosage unit is designed to contain

a specified quantity of medication for
ease and accuracy of dosage
administered.

 Each product is a formulation unique

unto itself
 Biopharmaceutic considerations often
determine the ultimate dose and dosage
form of a drug product.

☺ For example, the dosage for a drug

intended for local activity, such as a topical
dosage form, is often expressed in
concentration or as % of the active drug in
the formulation.
☺ The amount of drug is not specified
because it is the concentration of the drug
at the active site that relates to the
pharmacodynamic action.
Biopharmaceutics
 Biopharmaceutic studies must be.
performed to ensure that
 the dosage form does not irritate,
 cause an allergic response or
 allow systemic drug absorption.
The dosage of a drug intended for
systemic absorption is given on the basis
of absolute amount, such as mg or g.
c. route of administration

 each route of drug application presents

special biopharmaceutic considerations
in drug product design.
c. route of administration
 by carefully choosing the route of drug
administration and properly designing the drug
product, the bioavailability of the active drug
can vary from
 rapid and complete absorption to a
 slow, sustained rate of absorption or
 even virtually no absorption, depending on the
therapeutic objective.
Example

 An eye medication may require special

biopharmaceutic considerations including
appropriate
 pH,
 isotonicity,
 local irritation to the cornea,
 draining by tears, and
 concern for systemic drug absorption.
Scope of Biopharmaceutics

1. Encompasses all possible effects

observed
following the administration of the
drug
in the various dosage forms.
2. Encompasses all possible effects of
various
dosage forms on biological
response

3. Encompasses all possible

physiological
Pharmacokinetics:
 It is the study of kinetics of absorption,
distribution, metabolism and excretion.
 Elimination: It is combination of metabolism
and excretion.
 Drug disposition: The description of drug
distribution and elimination is often termed as
drug disposition.
 Clinical Pharmacokinetics: It is the
application of pharmacokinetic methods to drug
therapy.
Pharmacodynamics :
 Pharmacodynamics refers to the relationship
between the drug concentration at the site of
action(receptor) and pharmacologic response,
including biochemical and physiologic effects that
influence the interaction of drug with the receptor.
 Toxicokinetics: It is the application of
pharmacokinetic principles to the design, conduct
and interpretation of drug safety evaluation
studies and in validating dose related exposure in
animals.
.
 Clinical toxicology is the study of adverse effects of
drugs and toxic substances(poisons) in the body.
 Bioequivalent drug products: This term describes
pharmaceutical equivalent or pharmaceutical alternative
products that display comparable bioavailability when
studied under similar experimental conditions.
 Pharmaceutical Alternatives: Drug products that
contain the same therapeutic moiety but as different
salts, esters or complexes.
 E.g. Tetracycline phosphate or tetracycline
hydrochloride equivalent to 250 mg tetracycline base.
.
 Pharmaceutical equivalents: Drug products in
identical dosage forms that contain the same
active ingredients i.e. the same salt and ester,
are of the same dosage form, use the same
route of administration and are identical in
strength or concentration.(Excepients may vary)
 Therapeutic equivalents: Drug products are
considered therapeutic equivalents only if they
are pharmaceutical equivalents. FDA’s criteria is:
…
(1) they are approved as safe and effective;
(2) they are pharmaceutical equivalents in that they (a) contain identical
amounts of the same active drug ingredient in the same dosage form and
route of administration, and (b) meet compendial or other applicable
standards of strength, quality, purity, and identity;
(3) they are bioequivalent in that (a) they do not present a known or
potential bioequivalence problem, and they meet an acceptable in-vitro
standard, or (b) if they do present such a known or potential problem, they
are shown to meet an appropriate bioequivalence standard;
(4) they are adequately labeled; and
(5) they are manufactured in compliance with Current Good Manufacturing
Practice regulations. The FDA believes that products classified as
therapeutically equivalent can be substituted with the full expectation that
the substituted product will produce the same clinical effect and safety
profile as the prescribed product
…
 Therapeutic alternatives: Drug products containing
different active ingredients that are indicated for the
same therapeutic or clinical objectives.
 Active ingredients in therapeutic alternatives are from
the same pharmacologic class and are expected to
have the same therapeutic effect when administered
to patients for such condition of use.
 For example, ibuprofen is given instead of aspirin;
cimetidine may be given instead of ranitidine.
 A primary concern in
biopharmaceutics is the
bioavailability of drugs.

Bioavailability

refers to the measurement of the rate and extent

of active drug that reaches the systemic circulation.

means access to the bloodstream

Drug Bioavailability Process

Drug in the drug product

Solid drug particles

Drug in solution

Drug in the body

 Pharmaceutic Factors Affecting Drug
Bioavailability

1. type of the drug product

2. nature of excipients in the drug product
3. physico-chemical properties of the drug
- measurable characteristics by which a
compound interacts with other systems
Physico-Chemical Properties
of the Drug

1. Particle size of a drug in a solid dosage form

2. Particle size of a dispersed phase in an emulsion
3. Tablet disintegration
4. Tablet & capsule adjuncts
5. Tablet coating
6. Crystalline drug properties
Something to ponder….
1. Particle size of a drug in a solid
dosage form
 In order to affect dissolution rate based
on one’s objective, there should be a
change in particle size.
 ↓ particle size → larger surface area to
be wetted → ↑ dissolution rate → faster
rate of absorption
 But for local effect, increased particle
size is required
2. Particle size of the dispersed
phase in an emulsion
 2-phase system in which one should be
uniformly dispersed into another.

 Dispersed phase should be in small

particle size so it can readily mix with
dispersion medium.
3. Tablet Disintegration

 Disintegration is the physical break-up of

an intact dosage form to its component
aggregates.
 Disintegration depends on the
disintegrant used.
 Starch
 Microcrystalline cellulose
 It was generally recognized some years
ago that a solid drug product had to
disintegrate into small particles and
release the drug before absorption could
take place.
 For the purpose of monitoring tablet
disintegration, USP established an official
disintegration test.
USP Specifications

 Separate specifications are given for

 uncoated tablets
 plain coated tablets

 enteric coated tablets

 buccal tablets

 sublingual tablets
USP Specifications

 Solid drug products exempted from

disintegration tests
 Troches
 Tablets which are intended to be chewed
 Drug products intended for SR, or
prolonged or repeat action
4. Tablet & Capsule Adjuncts

 Excipients
– added to the active ingredient to
form a dosage form that is convenient for
control purposes.
- it should be inert, inactive, neither
enhances nor diminishes the therapeutic
effect of the drug
Roles/Effects of Excipients

1. may affect drug absorption

2. may increase solubility
3. may increase retention time of drug in the
GIT
4. may act as carriers to increase diffusion
across intestinal wall
 In contrast, most excipients may retard
drug dissolution and decrease drug
absorption
Different Excipients used in Tablets

1. Diluents – added to increase the bulk/mass

of the dosage form
 E.g. Lactose, Dibasic Ca Phosphate, starch,
microcrystalline cellulose
2. Binder – makes the diluent adhere to the
tablet to form a compact mass. Pressure is
applied to make the tablets contact.
 E.g Acacia, alginic acid, gelatin, povidone,
etc.
Different Excipients used in Tablets

 3. Lubricant
– helps to have an easier transfer from
one stage of manufacture to another
- assist the smooth tableting process.
 Ex. Mag. Stearate, stearic acid, talc,
hydrogenated vegetable oil
 excessive magnesium stearate (a hydrophobic
lubricant) in the formulation may retard drug
dissolution and cause slower drug absorption.
5. Tablet Coating
 protection
 uneven coating can cause uneven release of
active ingredient
 Example:
a. enteric coatings – employed to permit safe
passage of tablet through the acid environment
of the stomach where certain drugs may be
destroyed, to the more suitable juices of the
intestines where tablet dissolution safely takes
place. ( shellac, cellulose acetate phthalate)
 b. film-coatings
– employed to protect the drug substance
from the destructive influences of moisture, light
and air throughout their period of storage or to
conceal a bad or bitter taste from the taste buds
of the patient. (hydroxypropylmethylcellulose)

c. sugar-coatings – conceal bitter taste (liquid

glucose, sucrose)
.

4. Surfactants
Low conc. of surfactant = decrease
surface tension = rate of dissolution?
High conc. of surfactant = formation of
micelles = rate of dissolution?
6. Crystalline Drug Properties

 Polymorphism
– refers to the arrangement of a drug in various crystal
forms or Polymorphs
 Polymorphs
– have the same chemical structure but different
physical properties such as:
solubility, density, hardness and compression
characteristics
.
 Some polymorphic crystals may have
much lower aqueous solubility than the
amorphous forms, causing a product to
be incompletely absorbed.
Ex. Chloramphenicol

 Crystal with the LOWEST free energy is

stable
.

Solvate
Drug + solvent = crystal

Hydrates
Drug + H2O = crystal
 In general, the crystalline form of drugs are more
rigid and thermodynamically more stable than
the amorphous form. The crystal form with the
lowest free energy is the most stable polymorph.
 A change in crystal form may cause problems in
manufacturing the product. For example, a
change in crystal structure of the drug may
cause cracking in a tablet or even inability for a
granulation to be compressed to form a tablet.
Example
☺ Erythromycin dihydrate dissolves faster
than the monohydrate & anhydrous form

 less hydrated – faster dissolution

☺ Ampicillin anhydrous would have faster

dissolution than trihydrate but it is less
absorbed
Drugs with narrow therapeutic
window
 Size of dose (mg/kg)
 Dosing frequency (bid, tid, od)
Size of the dose

 Determined by:
 Inherent potency of the drug
 Dosing strengths

 E.g. score in tablets for fractured dosing.

Paper tablets
Dosing frequency

 Dependent on:
1. Clearance of the drug (elimination)
2. Target plasma drug concentration (MEC)
e.g. Drug with a short half-life or rapid
clearance  how frequent is the dosing?
Sustained release (SR) tablets

 Devised to minimize fluctuating plasma

concentration and good patient
compliance
Route of administration

Formulation given in IM, IV and oral only

changes the rate of absorption but NOT
the rate of elimination

Sublingual  rapid onset but shorter

duration of action
Terminologies
 THERAPEUTIC EFFECT:
 “The desired effect or beneficial effect of drug to the body is
called therapeutic effect”. 
 SIDE EFFECTS:
 In addition to therapeutic effects, a drug may also elicit
unwanted effects that in turn may cause complaints,
provoke illness, or even lead to death.
 “Any effect of drug other than desired effect is called side
effect”. If side effect is harmful it is called adverse effect
and if the side effect is lethal (cause death), it is called toxic
effect.
..
..

 - MEC:
 “It is the minimum concentration of drug that is required to
achieve the therapeutic effect”.
 - MTC:
 “It is the minimum concentration of the drug that is required to
produce toxic effects in the body”. 

 – HALF LIFE/ PLASMA HALF LIFE:

 “The Plasma half-life (t1/2) of a drug is the time taken for its
plasma concentration to be reduced to half of its original
concentration”.
t1/2 = 0.693/kel
..
 LADMER: The system which includes
liberation of a drug from the dosage form,"
absorption of the drug", distribution of the
drug", metabolism of the drug", excretion of
the drug and finally the response.
 The LADMER system is a way of
understanding what goes on in the body when
any compound that has an effect on the body
is administered or ingested.
..

 Volume of distribution:
 Vd has no direct physiological meaning
 it is not a ‘real’ volume and is usually referred
to as the apparent volume of distribution.
 It is defined as that volume of plasma in which
the total amount of drug in the body would be
required to be dissolved in order to reflect the
drug concentration attained in plasma.
..
 Clearance:
 Drug clearance (CL) is defined as the volume of plasma in the
vascular compartment cleared of drug per unit time by the
processes of metabolism and excretion. Clearance for a drug is
constant if the drug is eliminated by first-order kinetics. Drug can be
cleared by renal excretion or by metabolism or both. With respect
to the kidney and liver, etc., clearances are additive, that is:
 CLtotal = Clrenal+CLnonrenal
 Mathematically, clearance is the product of the first-order
elimination rate constant (k) and the apparent volume of distribution
(Vd). Thus
 CLtotal = k Vd
Thank
You!