2. ❑Dissolution is nothing but quality control tool.
❑Dissolution is solubilization of the solid dosage drug under
physiological conditions (GI track) after oral administrations.
❑In vitro dissolution may be relevant to the prediction of in vivo
performance.
What is dissolution ?
7. Factor influence the in vitro dissolution & their tolerance
Name Tolerance
Media Temperature (37 °C) ±0.5
pH ±0.05
Volume (%) ±1
Tem. During Vol. measurement (°C) 20-25
Time points (%) ±2
Replacement volume temp. (°C) ~37
RPM ±4
8. USE OF APPARATUS I & II
a. Conventional-release solid dosage forms
b. Prolonged-release solid dosage forms
c. Delayed-release solid dosage forms
10. LEVEL -1
No individual value lies outside each of the stated ranges and
no individual value is less than the stated amount at the final
test time.
Name Limit Explanation
Range 1 (20-30)% No sample lies outside the range
Range 2 (45-60)% No sample lies outside the range
Stated amount 80% No sample is less than 80%
RELEASE FOR PROLONG RELEASE SOLID DOSAGE
Continue…
11. LEVEL -2
The average value of the 12 units (L1 + L2) lies within each of the stated ranges and is not less than the
stated amount at the final test time; none is more than 10 per cent of labelled content outside each of the
stated ranges; and none is more than 10 per cent of labelled content below the stated amount at the final
test time
Name Limit Explanation
Range 1 (20-30)% Average release within the range & none is more than 10% of
outside the range.
Range 2 (45-60)% Average release within the range & none is more than 10% of
outside the range.
Stated amount 80% Average result not less than 80% but none is more than 10%
bellow from 80%.
12. LEVEL -3
The average value of the 24 units (L1 + L2 + L3) lies within each of the stated ranges, and is not less than the stated
amount at the final test time; not more than 2 of the 24 units are more than 10 per cent of labelled content outside
each of the stated ranges; not more than 2 of the 24 units are more than 10 per cent of labelled content below the
stated amount at the final test time;
and none of the units is more than 20 per cent of labelled content outside each
of the stated ranges or more than 20 per cent of labelled content below the stated amount at the final test time.
Name Limit Explanation
Range 1 (20-30)% Average release within the range & not more than 2 samples are
10% of outside the range but none is more than 20%.
Range 2 (45-60)% Average release within the range & not more than 2 samples are
10% of outside the range but none is more than 20%.
Final time 80% Average result not less than 80% & 2 samples are not more than
10% bellow from 80% but none is 20%.
13. RELEASE FOR DELATE RELEASE DOSAGE FORM
ACID STAGE
Level Units Explanation
A 1 6 No units exceeds 10% dissolved.
A 2 6 Average of 12 units NMT 10% dissolved & no units
exceeds 25%.
A3 12 Average of 24 units NMT 10% dissolved & no units
exceeds 25%.
14. FOR DELAYED RELEASE DOSAGE FORM
BUFFER STAGE
Level Units Explanation
B1 6 Each unit is NLT Q+5%.
B2 6 Average of 12 units is ≥Q dissolved & no units is <Q-
15%.
B3 12 Average of 24 units is ≥Q dissolved & two units are
<Q-15% but & no units is <Q-25%.
15. DISSOLUTION PROFILE COMPARISONE
1. For Preapproval (Test & RLD) &
2. For Post approval (Test & Test)
For Post Approval Changes
a. Scale-up
b. Manufacturing site changes,
c. Component and composition changes
d. Equipment and process changes
❑ In the presence of certain minor changes, the single-point dissolution test may be adequate to ensure unchanged
product quality and performance.
❑ For more major changes, a dissolution profile comparison performed under identical conditions for the product
before and after the change(s) is recommended
16. The dissolution profile comparison may be carried out using following methods
❑ Model Independent Approach Using a Similarity Factor
❑ Model Independent Multivariate Confidence Region Procedure
❑ Model Dependent Approaches
Model Independent Approach Using a Similarity Factor
➢ A difference factor (f1 ): 0-15
➢ A similarity factor (f2): 50-100
➢ 12 units for each of the test & reference
➢ Time points should be 15, 30, 45 & 60 min
➢ %RSD : Initial time point is NMT 20%, other time points NMT 10%
It recommends dissolution profile comparisons using a model independent
approach and the similarity factor (f2).
