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Dissolution: Lynda Paleshnuik
Dissolution: Lynda Paleshnuik
Lynda Paleshnuik
Training workshop: Training workshop on regulatory requirements for registration of Artemisinin based combined medicines and
. assessment of data submitted to regulatory authorities, February 23-27, 2009, Kampala, Uganda
Overview
Disintegration vs Dissolution
USP <1088>:
and
Starting point:
http://www.who.int/phint/en/p/docf/
https://www.who.int/medicines/publications/pharmacopoe
ia/mono_dev/en/index.html
PhInt monographs are available for all APIs and for the
following FPPs:
Single-API FPPs
Artemether capsules
Artemether tablets
Artesunate tablets
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
7|
PhInt Monographs and Requirements
Monographs in progress:
Amodiaquine tablets
Sulfadoxine/Pyrimethamine tablets.
Mefloquine tablets
Liquid preparations for oral use under the section, Powders for
oral solutions/suspensions/drops
BP 2008: no monographs.
USP 2009:
Dosage Forms:
Amodiaquine HCl Tablets
Sulfadoxine/Pyrimethamine Tablets
Sulfadoxine/Pyrimethamine Tablets
Medium: pH 6.8 phosphate buffer, prepared as directed under Buffer
Solutions in the section Reagents, Indicators, and Solutions; 1000 mL.
Apparatus 2: 75 rpm.
NLT 60% (Q) each API in 30 minutes.
(The above are in USP 2009 and USP 2009 S1)
pH 6.8 buffer
pH 4.5 buffer
Calculation of similarity:
1) Purpose of study
6) Conclusion/recommendation
a) discriminating, and
Factors to consider:
Manufacturing parameters:
Lubrication
Blend time
Compression force
Drying parameters
Solubility
pH
API quantitation
Solubility:
API quantitation:
UV is often used; for UV the applicant should have demonstrated:
a) non-interference with formulation components (spectra of API in
the formula and in standard solutions should be identical in
shape/magnitude);
b) linearity (absorbance vs concentration) up to the highest expected
concentration.
Note that these will be determined as part of routine validation.
Chromatography is often necessary instead of UV when there is
excipient interference, it is low dose or it is a FDC-FPP that
requires more sensitivity and/or selectivity.
- Resolution (>2)
Apparatus
Calculations
Acceptance Criteria
Filtration:
Stability of samples:
Check:
4) Published methods
Paddle, 75 rpm
or
DT NMT 10 min
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
47 |
Justification Based on Results
% released: 15 33 49 68 83 98 102
For the 7 APIs in the ACTs, the only hit on the FDA site
is for mefloquine HCl tablets:
Apparatus: Basket
Validation:
Specificity
Linearity
Accuracy
Repeatability
Intermediate precision
Precision:
System precision
Repeatability determination:
OR
OR
Intermediate Precision:
Example 1:
Example 2