Bioavailability and bioequivalence testing

Bioavailability and bioequivalence testing

1. BIOAVAILABILITY AND BIOEQUIVALENCE TESTING Presented by N.Lakshmi Priya Pharmaceutics M.Pharmacy

2. INTRODUCTION Introduced in 1945. Studies of relative absorption of vitamins. Referred as physiologic availability.

3. CONCEPT OF BIOAVAILABILITY? I ncreased prescriptions. Formulary systems. Extending the laws of pharmacist’s role. By US federal government.

4. DEFINITION: Relative amount of an administered dose that reaches the systemic circulation. OR Rate and extent of absorption of unchanged drug from its dosage form. bioavailable dose administered dose F =

5. OBJECTIVES: suitable dosage form. efficiency of absorption. New formulations. Control of quality

6. TYPES OF BIOAVAILABILITY 1.Absolute bioavailability Plasma concentration versus time data Urinary data

7. 2.RELATIVE BIOAVAILABILITY Plasma concentration v s time data. Urinary data

8. FACTORS AFFECTING BIOAVAILABILITY FORMULATION FACTORS EXCIPIENTS NATURE OF THE DRUG PARTICLE SIZE FORM OF THE DRUG PHYSIOLOGICAL FACTORS GASTRIC EMPTYING INTESTINAL MOTILITY PH INTESTINAL WALL CHANGES

9. CRITERIA FOR BIOAVAILABILITY TESTING 12 subjects. Physical examination and laboratory testing. Cross over design.

10. MEASUREMENT OF BIOAVAILABILITY Pharmacokinetic methods Plasma level time studies Urinary excretion studies Pharmacodynamic methods Acute pharmacologic response Therapeutic response

11. PHARMACOKINETIC METHODS 1.Plasma level time studies 3 parameters are to be considered. C max. t max. AUC

12. 2.URINARY EXCRETION STUDIES. 3 parameters are to be considered . dX u /dt (t u ) max X U

13. ACUTE PHARMACOLOGIC RESPONSE ECG or EEG, pupil diameter is related to time course of a given drug. time Dose

14. DISADVANTAGES Variable Difficulty in correlation Response is not due to the pharmacological effect.

15. 2.THERAPEUTIC RESPONSE Clinical response to a given formulation . Drawback: Quantitation is improper to assess the relative bioavailability .

16. OTHER MEASURES 1.DISSOLUTION RATE In-vitro dissolution testing models. Factors to be considered. Dissolution apparatus Dissolution fluid Process parameters

17. TYPES OF DISSOLUTION APPARATUS Closed -compartment Open-compartment Dialysis systems ROTATING BASKET ROTATING PADDLE

18. IN VITRO-IN VIVO CORRELATION Objectives Batch to batch consistency developing a new dosage form Basic approaches By linear relations ship By using previous data

19. QUANTITATIVE INVITRO-INVIVO CORRELATIONS Based on plasma level data Based on urinary excretion data Based on pharmacologic response

20. STATISTICAL TERMS Average ANOVA Bar over a letter Bioequivalence Confidence interval Control Cross over Distribution Formulation

21. Frequency distribution Logarithmic transformation Mean Median Period Sequence group Standard error washout

22. BIOEQUIVALENCE Drug substance in two or more identical dosage forms reaches the systemic circulation at same relative rate and extent. RELATED TERMS Pharmaceutical equivalence Chemical equivalence Therapeutic equivalence

23. MEASUREMENT OF BIOEQUIVALENCE Same route,equal doses,different times. Study in healthy, adult male volunteers. Latin square cross over design

24. ADVANTAGES Minimises intersubject variability. Minimises variations Minimises carry over effects . DRAWBACKS Long time Dropout Rates are high

25. Statistical interpretation of analysis data. ANOVA CLINICALLY SIGNIFICANT

26. METHODS FOR ENHANCMENT OF BIOAVAILABILITY Micronization Use of surfactants Use of salt forms Alteration of pH of the drug micro environment Use of metastable polymorph Solute-solvent complexation Solvent deposition

27. Selective adsorption on insoluble carriers Solid solutions Eutectic mixtures Solid dispersions Molecular encapsulation with cyclodextrins

28. REFERENCES Biopharmaceutics and pharmacokinetics- D.M BRAHMANKAR. Page no:282-302 Biopharmaceutics and pharmacokinetics- P L MADHAN Page no:125-178 Basic pharmacokinetics- SUNIL S JAMBHEKAR AND PHILIP J BREEN page no:458-470