Professional Documents
Culture Documents
Continuing Equivalence
Erika Stippler, Ph.D.
BCS Concept
Published
Solubility
High
Low
High
Low
Permeability
High
High
Low
Low
Human Permeability
10
Gastric emptying
determines on-set of
absorption
II
Dissolution likely
to be rate limiting
1.0
III
IV
0.1
Generally problem
molecules
0.01
1
10
100
1000
10000
100000
EMA
WHO
Apparatus
USP App. 1
USP App. 2
Basket
Paddle
Basket
Paddle
Dissolution
media
Buffer pH 1.2
Buffer pH 4.5
Buffer pH 6.8
Absolutely no addition
of surfactant or
enzymes is allowed
Volume
900 ml
900 ml or less
900 ml or less
Temperature
37C 0.5C
37C 1C
37C
Agitation
Sampling time
Sample #
12
12
12
Requirements
f2 50
50 f2 100
50 f2 100
EMA
WHO
Very rapidly
dissolving
No definition
Rapidly
dissolving
No definition
Similarly
dissolving
(EMA)
No definition
No definition
Test conditions
Paddle at 50 rpm or
Basket at 100 rpm in
900 ml or less of
0.1N HCl or SGF
Buffer pH 4.5
Buffer pH 6.8 or SIF
Paddle at 50 rpm or
Basket at 100 rpm in
900 ml or less of
0.1N HCl or SGF
Buffer pH 4.5
Buffer pH 6.8 or SIF
Paddle at 75 rpm or
Basket at 100 rpm in
900 ml or less of
Buffer pH 1.2
Buffer pH 4.5
Buffer pH 6.8
BCS-Class
I drug substance
Rapidly dissolving IR drug product
Test and reference drug product are pharmaceutically equivalent
Test and reference drug product exhibit similar dissolution profiles
Exclusions
IR
II
BCS-Class I drugs
very rapidly dissolving drug products (both test and reference)
rapidly dissolving drug products for which similarity of dissolution profiles was
demonstrated
Case
About
Using
There
NEW
Non-solution
Aqueous
Dissolution Conditions
cases possible
Conduct dissolution tests
To
perform optimally or
To be optimally available for in vivo absorption
Pharmaceutically equivalence