Bioavailability (BA) studies play a major role in the drug development phase for both new drug products and their generic equivalents, and thus attract considerable attention globally. There are several approaches to assess BA and each regulatory authority has its own regulations/guidance for conducting BA studies before approving generic products for marketing in their country. Therefore, a thorough understanding is required of these BA concepts and basic regulatory considerations for conducting BA studies. This article briefly reviews the BA concepts, approaches, designs, and conducting and analysis of data obtained. INTRODUCTION • Bioavailability means the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action. • Results in 100% bioavailability as the absorption process is bypassed. • The absolute bioavailability of a drug, when administered by an extra vascular route is usually less than one (i.e. F<100%).> Oral > Rectal > Topical. A systematic approach to ensure bioavailability of pharmaceutical products: BIOAVAILABILITY It the degree to which, or the rate at which, a medication or other substance is absorbed or becomes available at the targeted place in the body. Bioavailability can be influenced by inactive ingredients (see Excipients) in the drug such as additives that prevent the medication from dissolving in the stomach. If a medication that is intended to be taken on an empty stomach is taken instead with food, this can also change the absorption rate and affect the bioavailability of the active ingredient BIO AVAILABILITY FRACTION (F): Bio available fraction it refers to the fraction of administered dose that enters the systemic circulation. *100

1. BIOAVAILABILITY STUDIES
P. Swapna
Department of Pharmaceutics
St. Peter’s College of Pharmacy
Guide: G.Sandeep, Assisstent professor.

3. Definition
 Bioavailability is defined as the rate at which a medication or
active ingredient or active moiety is absorbed from a drug
product and become available at the targeted place in the
body. (2)

4. Representation of Bioavailability(2)

5. Bioavailability fraction
*100
F = Bioavailable dose
Administered dose

6. Types of bioavailability
 Relative bioavailability
Absolute bioavailability
Absolute
bioavailability =
Relative
bioavailability =

7. Percent relative bioavailability
It is calculated from urinary excretion data.
Percent relative availability =

8. Objectives of bioavailability
Bioavailability studies are important in the —
 Primary stages of development of a suitable dosage form.
 Determination of influence of excipients, patient related factors.
 Development of new formulations of the existing drugs.
 Control of quality of a drug product during the early stages of marketing.
 Comparison of availability of a drug substance from different dosage
forms.

9. Factors influencing Bioavailability
 Physico chemical factors
 Patient related factors
 Route of administration

10. Bioavailability study protocol
1. Study objective
2.Study design
 Experimental design
 Wash out period
 Drug products
 Administration of dose
 Selection of subjects
Assessment of bioavailability
 Study conduct
 Study method
 Statistical analysis of data

11. Experimental design
 Parallel design
 Cross over design
(i) Latin square cross over
design
(ii) Balanced incomplete
block design

12. Experimental design
Parallel study design
 Aviod the bias
Disadvantages
 Inter subject variations is
not corrected.
Cross over study design
 Minimizes the inter
subject variations.
Types
 Latin square cross over
design.
 Balanced incomplete
block design.

13.  Parallel study design
Two formulations
h healthy volunteers
Randomisation
therapueticsupratherapuetic
effect
wash out period
Cross over study design
One formulation
`
1 period
subjects(control)
wash out period

14. Types of cross over design
Two-way Crossover
Group No. Subjects in Group Treatment for Period No.
1.
2.
1,2,3,4,5,6
7,8,9,10,11,12
I II
A B
B A
Three-Way Crossover
Group No. Subjects in Group Treatment for Period No.
I II III
1.
2.
3.
1,2,3,4,5,6
7,8,9,10,11,12
13,14,15,16,17,18
A C B
B A C
C B A
Four-Way Crossover
Group No. Subjects in Group Treatment for Period No.
1.
2.
3.
4.
1,2,3,4,5,6
7,8,9,10,11,12
13,14,15,16,17,18
19,20,21,22,23,24
I II III IV
A B C D
B D A C
C A D B
D C B A

15. Latin square study design
 Subject itself acts as his
control in Latin square design.
Advantages
 Minimizes carry over
effect.
 Minimizes time effect on bioavailability.
Disadvantages
 Requires long time since a wash out
period exists between two study periods.
More no.of formulations, more subject
dropouts and study becomes difficult.

16. Balanced incomplete block design
Sailent Features
I. Each subject receives not more
than two formulations.
II. Each formulation is administered
the same no.of times.
III. Each pair of formulations occurs
together in the same no.of
subjects.
Subject Treatment For Period No.
1
2
3
4
5
6
7
8
9
10
11
12
I
A
B
A
C
A
D
B
C
B
D
C
D
II
B
A
C
A
D
A
C
B
D
B
D
C

17. wash out period

18. Drug products
 Generic products
 Reference products

19. Routes of administration
Administration of dose
Single dose
Multiple dose

20. Bioavailability studies generally involve the following
 Selection of subjects
 Monitoring the health of the
subjects
 Human volunteers
Health subjects vs Patients

21. Assessment of bioavailability
Parameters to be
assessed
AUC
Cmax
Tmax
T12
Kel

22. Study
conduct
Selection of dose
Sampling times
Sample fluids and
their collection.

23. Study method
 Pharmacokinetic methods
 Plasma level time studies
 Urinary excretion method
 Pharmaco dynamic methods
 Acute pharmacological responses
 Therapuetic responses

24. Statistical analysis of data
 Analysis of variance
 Confidence interval

25. CONCLUSION

26. References
1. Brahmankar, Sunil. Jaiswal, Biopharmaceutics and pharmacokinetics a treatise,
edition-2, published in 1995. pg.no: 315-325.
2. Leon Shargel, Susanna Wu-Pong, Andrew B.C. Yu Applied Biopharmaceutics &
Pharmacokinetics, 5th Edition August 2004.
3. Milo Gibaldi, Biopharmaceutics and clinical pharmacy, edition-4, published in
1991. Pg. No.147-149,155.
4. V. Venateshwarlu, Biopharmaceutics and pharmacokinetics, 2004 edition.
5. Dr. Anant Pardhakar, Sunil Bakliwal, Biopharmaceutics And Pharmacokinetics ,
edition-2, published in october 2006.