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1. 1
Definitions
• Biopharmaceutics is the study of the
physicochemical properties of the drug and
the drug product, in vitro, as it relates to the
bioavailability of the drug, in vivo, and its
desired therapeutic effect
• Biopharmaceutics thus links the physical and
chemical properties of the drug and the drug
product to their clinical performance, in vivo

2. 2
• a primary concern in biopharmaceutics is the
bioavailability of drugs. Bioavailability refers
to the measurement of the rate and extent of
active drug that becomes available at the site
of action.
• For the majority of orally administered drugs,
the site of action is within the systemic
circulation and the drug must be absorbed to
achieve a pharmacological response

3. 3

4. 4
Other routes
• A drug product may also be designed to deliver the drug
directly to the site of action before reaching the systemic
circulation, which is often termed locally acting drug.
• Examples: ophthalmic, pulmonary, and nasal drug products.
• Similar to systemic bioavailability, local drug bioavailability is
strongly influenced by physicochemical properties of the drug
and drug product, the rate and extent of drug release from
the drug product, and permeation at the target site (eg, skin
physiology compared with that in the cornea).

5. Major goal
• Biopharmaceutics aims to balance the amount
and extent of drug delivered from the drug
product to achieve
– optimal therapeutic efficacy and
– safety for the patient
5

6. 6
Biopharmaceutics allows for the rational design of
drug products and is based on:
• The physical and chemical properties of the drug substance
• The route of drug administration, including the anatomic and
physiologic nature of the application site (eg, oral, topical,
injectable, implant, transdermal patch, etc)
• Desired pharmacodynamic effect (eg, immediate or
prolonged activity)
• Toxicological properties of the drug
• Safety of excipients
• Effect of excipients and dosage form on drug product
performance
• Manufacturing processes

7. 7
Topical/ local action
• Some drugs are intended for topical or local
therapeutic action at the site of administration.
• Drugs intended for local activity are designed to have a
direct pharmacodynamic action without affecting other
body organs, and systemic drug absorption is often
undesirable.
• Locally acting drugs may be administered orally (eg, local
GI effect) or applied topically to the skin, nose, eye,
mucous membranes, buccal cavity, throat, or rectum

8. 8
• By choosing the route of drug administration carefully and
properly designing the drug product, the bioavailability of the
active drug can be varied from rapid and complete
absorption to a slow, sustained rate of absorption or even
virtually no absorption, depending on the therapeutic
objective.
• Once the drug is systemically absorbed, normal physiologic
processes for drug distribution and elimination occur.
• These intrinsic factors may also be influenced by the
specific formulation of the drug (eg, encapsulated drug
in liposome or microspheres may change the drug
distribution and systemic clearance).

9. 9
Rate-limiting steps (RLS) in drug
absorption
• For solid oral, immediate-release drug products (eg, tablets,
capsules), the rate processes include
(1)disintegration of the drug product and subsequent release
of the drug,
(2) dissolution of the drug in an aqueous environment, and
(3)absorption across cell membranes into the systemic
circulation.
The rate at which drug reaches the circulatory
system is determined by the slowest step in
the sequence.

10. Common Scenario for IMDFs
• Dissolution is usually RLS for drug with very
poor aqueous solubility.
• Rate at which the drug crosses or permeates
cell membranes is RLS drug that has a high
aqueous solubility
10

11. Disintegration
• For immediate-release, solid oral
dosage forms, the drug product
must disintegrate into small
particles and release the drug.
• Complete disintegration is defined
by the USP-NF (National Formulary)
as “state in which any residue of
the unit, except fragments of
insoluble coating or capsule shell,
remaining on the screen of the
test apparatus or adhering to the
lower surface of the disk, if used,
is a soft mass having no palpably
firm core.”
• What are solid oral DFs
exempted from disintegration?? 11

12. USP disintegration apparatus
Question:
In which cases disintegration
testing can be used in lieu of
dissolution testing?
12

13. 13
Dissolution and Solubility
• Solubility will be covered in more details later
• Dissolution is the process by which a solid drug
substance becomes dissolved in a solvent over
time.
• Solubility by definition is an equilibrium property,
whereas dissolution is a dynamic property.
• In biologic systems, drug dissolution in an
aqueous medium is an important prior condition
for predicting systemic drug absorption.

14. 14

15. Dissolution apparatus USP
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16. 16

17. Physicochemical Properties of Drug
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18. Solubility, pH, and Drug Absorption
• The solubility–pH profile is a plot of the
solubility of the drug at various physiologic pH
values
18

19. 19
Stability, pH, and Drug Absorption
• stability–pH profile is a plot of the
reaction rate constant for drug
degradation versus pH
• If drug decomposition occurs by acid
or base catalysis, some prediction of
degradation of the drug in the
gastrointestinal tract may be made.

20. Stability–pH profile of erythromycin
What should we do?
20

21. 21
Particle Size and Drug Absorption
• Dissolution kinetics is also affected by particle
size.
• As described in the Noyes–Whitney dissolution
model, the dissolution rate is proportional to the
surface area of the drug
• The effective surface area of a drug is increased
enormously by a reduction in the particle size
• Griseofulvin, nitrofurantoin, and many steroids
are drugs with low aqueous solubility; reduction
of the particle size by milling to a micronized
form has improved the oral absorption of these
drugs
Nanosizing: even sometimes better

22. 22
Polymorphism, Solvates, and Drug Absorption
• Polymorphism refers to the arrangement of a
drug substance in various crystal forms or
polymorphs
• A drug that exists as an amorphous form (non-
crystalline form) generally dissolves more
rapidly than the same drug in a more
structurally rigid crystalline form
• Some polymorphs are metastable and may
convert to a more stable form over time

23. Chloramphenicol polymorphism and F
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