This document compares the bioavailability of single dose versus multiple dose drug formulations. It discusses factors that influence bioavailability such as pharmaceutical properties, patient characteristics, and route of administration. Single dose studies are commonly used but cannot predict steady state levels, while multiple dose studies provide a more accurate clinical description but are more complex. The document outlines study designs including parallel and crossover designs and considerations for single and multiple dose bioavailability studies. In conclusion, both study types have advantages and disadvantages depending on the drug and study objectives.

1. Presented By
Arantha.J.Joseph
1st Year Mpharm
Dept.Of Pharmaceutics 1

2. COMPARISON OF BIOAVAILABILITY OF
SINGLE DOSE VS MULTIPLE DOSE
FORMULATIONS
2

3. 3

4. FACTORS
Pharmaceutical
factors.
Patient related
factors.
Route of administration.
4

5. COMPARATIVE BIOAVAILABILITY:
When the systemic availability of a drug after oral
administration is compared with that of an oral standard of
the same drug
 Fr
5

6. WHY ARE WE
CONDUCTING SUCH
STUDIES ???
6

7. 7
 Determination of influence of excipients, patient related
factors and possible interactions.
 Development of new formulation of existing drug.
 Control of quality of drug product during early stages of
marketing .
Comparison of availability of a drug substance from
different dosage forms or from the same dosage form
produced by different manufacturers.

8. SINGLE DOSE VS MULTIPLE DOSE
8

9. 9

10. 10

11. 11

12. STUDY DESIGNS
Selection of study design is based upon .
 Number of formulations to be compared.
 Characteristics of the drug and disposition.
 Study objective.
 Availability of the subject.
 Inter and intra subject variability.
 Duration of study or the number of periods allowed.
 Cost of adding a subject relative to that of
adding one period.
12

13. BIOAVAILABILITY STUDIES
1. Parallel design
2. Cross over design
i. Latin square cross over design
ii. Balanced incomplete block
design
iii .Replicated cross over design
13

14. PARALLEL DESIGN
14

15. CROSS OVER DESIGN
LATIN SQUARE CROSS OVER DESIGN
15

16. BALANCED INCOMPLETE CROSS OVER DESIGN
16

17. REPLICATED CROSS OVER DESIGN
17

18. GENERAL APPROACHES FOR SINGLE
DOSE STUDY
Generally the highest marketed strength should
be administered as a single unit.
If necessary for analytical reasons multiple units
of highest strength can be administered.
 Providing the total single dose remains within
the labelled range.
18

19. The lot numbers of both test and reference listed.
Expiration date for the reference product should be
stated.
 The drug content of the test product shouldn’t
differ from reference product by more than 5%.
An adequate washout period should (more than
5half life) separate each treatment.
19

20. Prior and during each study phase
Subjects should be allowed water as desired
except for 1hr before .
After drug admn; be provided standard meals
not less than 4hrs.
 Abstain from alcohol for 24hrs prior to each
study period and until after the last sample from
each period is collected.
20

21. MULTIPLE DOSE
Very potent or toxic drugs
Single dose study cannot be conducted in healthy
volunteers – tolerability reasons
Multiple dose study can be used
21

22. In rare situations problems of sensitivity of the analytical
method sufficiently precise plasma concentration
measurements after single dose administration.
Where the con at steady state is sufficiently high to
measure.
Multiple dose study - alternative
22

23. 23

24. Problems in plasma concentration measurement after
single dose .
Intra individual variability in the plasma
concentration or disposition rate is inherently large.
In the case of extended release formulations (in
addition to single dose studies).
24

25. If special dosage regimens such as
loading dose or twice a day dosing
are to be used.
Differences in rate of absorption but
not in the extent of absorption
Eg : Rivastigmine tartarate(oral
cap), Quatiapine fumerate(oral tab)
25

26. 26
conclusion

27. ADVANTAGES
SINGLE DOSE
Very common.
Easy.
Less exposure to lugs.
Less tedious.
MULTI DOSE
More accurate clinical
description.
Fewer blood samples are
required .
Drug levels are high
27

28. DISADVANTAGES
SINGLE DOSE
Cannot predict steady
state predictions.
Inter subject variability
cannot be predicted.
Long sampling periods.
MULTIDOSE
Tedious
Costly and difficult to
conduct.
Poor compliance by
subjects .
More exposure to test
drugs hence potential for
ADR.
28

29. REFERENCE
D.M .Brahmankar,Sunil B Jaiswal,Biopharmaceutics and
Pharmacokinetics 2nd edition ,pg no 315-363.
Attachment 1 of Division-Notification 0229 No. 10 of the
Pharmaceutical and Food Safety Bureau, dated February
29, 2012
Xue-Jia Zhai, MD, Ye Yu, MD, Fen Chen, MS, Yong-Ning
Lu, MD, ; Comparative Bioavailability and Tolerability of
Single and Multiple Doses of 2 Diclofenac Sodium
Sustained-Release Tablet Formulations in Fasting, Healthy
Chinese Male Volunteers ,Sciecedirect ;1-09-2013
29

30. Henry.J.Malinowski;Bioavailability and Bioequivalence
testing; Remington’s textbook of pharmaceutics ;
volume 1; chapter 53 ; pg no 995 -1004
Applied Biopharmaceutics and Pharmacokinetics-5th
edition by Leon Shargel, Susanna Wu-PONG, Andrew
B.C.YU. Page no; 453-498
Alfredo García ; Design of Bioequivalence Studies
WHO Workshop on Assessment of Bioequivalence
Data, 31 August – 3 September, 2010, Addis Ababa
30

31. THANKUUUUUU…….
31