C.

Bioequivalence :- It is a relative term which denotes that the

drug substance in two or more identical dosage forms, reaches
the systemic circulation at the same relative rate and to the
same relative extent i.e. their plasma concentration-time
profiles will be identical without significant statistical
differences.
When statistically significant differences are observed in the
bioavailability of two or more drug products, bio
inequivalence is indicated.
Types Of Bioequivalence Studies:
Bioequivalence can be demonstrated either -

In vivo, or

In vitro.
rIn vivo biocquivalence studies are conducted in the
usual manner as discussed for bioavailability
studics, i.c. the pharmacokinetic and the
pharmacodynamic methods.

1. Pharmacokinetic Methods
a) Plasma level-time studies
b) Urinary Excretion studies
2. Pharmacodynamic Methods
a) Acute pharmacological response
b) Therapeutic response
Types of test designs
1.Completely randomized designs
Alltreatments( factor levels) are randomly allocated among all
Experimental subjects.
Method of randomization : label all subjects with the same number
digits. Randomly select non-repeating numbers.
Advantages:
Easy to construct.
 VAny number of treatments & subjects.
VEasy &simple to analyses.
Disadvantages:
V
Best suited for relatively few treatments.
V
All subjects must be as homogenous

2. Randomized block designs

Subjects are sorted into homogenous groups called blocks.

Method of randomization: Subjects having similar background

characteristics are formed as blocks.
 Then treatments are randomized within each block, just like the
simple randomization.
Advantages:
Effective & systemic way of grouping.
Any number of treatments or replications.
V
Different treatments need not have equal sample size.
Statistical analysis simple &easy toconstruct.
Spoiled results, the design is easy to construct.
Disadvantages:
VMore complexanalysis
VDegrees of freedom of experimental error are not as large as
with a completely randomised design.
Repeated measures, cross-over & carry-over designs:
Same subject serves as a block.
Repeated measures on each subject we get the design name
"repeated measures design"
The administration of two or more treatments one after the other in
a specified or random order to the same group of patients is called
a crossover design or change-over design
Carry over effects
Wash out period
Advantages:
vGood precision for comparing treatments
VEconomic on subjects
Disadvantages:
Order-effect.
Carry over effect.
Latin Square designs:
Each Subject receives each treatment during the course of the
experiment.
A Latin square design is a two factor design with one
observation in each cell.
Rows represent subjects &columns represent treatments.
Standard: the first row & the first column consistr letters in
alphabetical order.
|Latin-Square Crossover Design for a Bioequivalence Study of Three
Drug Products in Six Human Volunteers

Drug Product
Subject Study Washout Study Washout Study
Period1period1 Period 2 period 2 Period 3
1 A B C
2 B C A
3 C A B
4 A C B
5 C B A
6 B A C
Advantages:
VMinimizes inter-subject variability, Intra-subject variability &
time effect.
Formulation variables.
Disadvantages:
Degrees of freedom for experiments error larger than
necessary.
More complex.
Wash out period very long