1. Biopharmaceutics 4th year

2. Biopharmaceutics: is defined as the study of factors influencing the rate and amount of drug that reaches the systemic circulation. Absorption is the process of movement of drug from its site of administration to systemic circulation. Bioavailability is defined as the rate and amount of drug that reach systemic circulations

3. Drug Absorption and Bioavailability
The oral route of drug administration is the most
common for systemically acting drugs. To
achieve the desired therapeutic objective, the
drug product must deliver the active drug at an
optimal rate and amount.

4. Drug absorption and Bioavailability
After oral administration of solid dosage form the drug undergo the following steps

5. Drug absorption and Bioavailability
After oral administration of solid dosage form the drug undergo the following steps:
Disintegration of drug product
Deaggregation and release
Dissolution
Movement of the dissolved drug to systemic circulation

6. Factors affecting GI absorption of drug
Physicochemical factors
Dosage form factors
Patient related factors

7. Factors affecting GI absorption of drug
Physicochemical Factors

8. 1) Drug solubility and dissolution rate
Events that occur after oral administration of solid dosage form

9. 1) Drug solubility and dissolution rate
The two rate determining process in orally administered drug are
Rate of dissolution
Rate of permeation

10. 1) Drug solubility and dissolution rate
-Dissolution is RDS in hydrophobic drug - If drug is hydrophilic dissolution is rapid but permeation through biomembrane is said to be RDS.

11. 2)Particle size and effective surface area
-Particle size and effective surface area are inversely related to each other.
-Effective surface area??
-According to Noyes-Whitney
equation
- Greater the effective surface area, more the
contact between the solid surface and the
aqueous solvent and faster dissolution.

12. 2)Particle size and effective surface area
-Reduce in particle size can be done by micronization.
-Particle size reduction is not always advisable especially when the drugs are unstable and degrade in solution form (penicillin G and erythromycin) or produce undesirable effect like gastric irritation (nitrofurantoin).

13. 3) Polymorphism and Amorphous
Depending on internal structure , solid can exist as crystalline or amorphous when a substance exist in more than one crystalline form is known as polymorph and the phenomena known as polymorphism

14. 3) Polymorphism and Amorphous
Polymorphs differ in their physical properties:
Solubility
Melting point
Density
Hardness
Compression characteristics

15. 3) Polymorphism and Amorphous
Depending on stability:
Stable polymorph :
Lowest energy state
High melting point
Least aqueous solubility
Metastable polymorph:
higher energy state
lower melting point
High aqueous solubility

16. 3) Polymorphism and Amorphous
-Since metastable have greater aqueous solubility show better bioavailability and are more preferred in formulations -Metastable on aging convert to less soluble stable -This conversion can be inhibited by dehydration of the environment or adding viscosity building agent such as PVP , gelatin….

17. 3) Polymorphism and Amorphous
Amorphous have higher aqueous solubility than crystalline form
Order of dissolution of solids
Amorphous > metastable> stable

18. 4) Hydrate/Solvate
-the anhydrous form of the drug has greater aqueous solubility than the hydrates .
-The hydrate is already in interaction with water so has less energy to break up than the anhydrates
The anhydrous form of theophylline and ampicillin have
greater aqueous solubilities
Dissolve at faster rate
Show better bioavailability
In comparison to monohydrate and trihydrate form respectively.

19. Most of drug are either weak acid or weak base
5) Salt form of drug
Most of drug are either weak acid or weak base
To enhance their solubility and dissolution rate they converted to their salt form

20. 5) Salt form of drug
With weak acidic drug a strong base salt is prepared e.g. sodium or potassium salt
With weak basic drug a strong acid salt is prepared e.g. HCL salt or sulfate salt

21. 5) Salt form of drug
-In the case of salt of weak acid the pH of the diffusion layer will be higher than that of free acid -Due to high pH of the diffusion layer solubility and dissolution of weak acid occur

22. 5) Salt form of drug
-In the case of salt of weak base the pH of the diffusion layer will be lower than that of free base -Due to low pH of the diffusion layer solubility and dissolution of weak base is enhanced

23. 5) Salt form of drug

24. 6) Drug pKa and Gastrointestinal pH
- Most drugs are weak acid or weak base
- undergo ionization at pH of biological fluid
Only unionized drug if its lipid soluble can permeate the membrane
Amount of unionized drug depend on pKa and pH of biological fluid

25. 6) Drug pKa and Gastrointestinal pH
-the amount of ionized and unionized drug can be determined by
Henderson-Hasselblach equation
For weak acids

26. 6) Drug pKa and Gastrointestinal pH
Henderson-Hasselblach equation
For weak bases

27. 6) Drug pKa and Gastrointestinal pH

28. 6) Drug pKa and Gastrointestinal pH

29. 7) Lipophilicity and drug absorption
- if the drug exists in unionized form it will be poorly absorbed if it has poor lipid solubility
ideally, the drug should have sufficient aqueous solubility to dissolve in the fluids at the site of absorption and
High lipid solubility to facilitate the partitioning of drug through biomembranes to systemic circulations