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?
Increased 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 vs 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.
Cmax.
tmax.
AUC

13. 2.URINARY EXCRETION
STUDIES.
3 parameters are to be considered.
dXu/dt
(tu)max
XU

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

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

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

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

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

20. 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

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

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

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

24. 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

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

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

27. Statistical interpretation of
analysis data.
ANOVA
CLINICALLY SIGNIFICANT

28. 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

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

30. 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