One major criterion for selecting the QC dissolution method should be its discriminatory power to show changes in the critical attributes of the release mechanism of the chosen formulation.
The discriminatory power is the ability of a test procedure to discriminate between batches manufactured with different critical process parameters and /or critical material attributes which if altered, may have an impact on the bioavailability.
Ideally all non-bioequivalent batches should be detected by the in-vitro dissolution test results. To ensure that the results of the bioequivalence study may be extrapolated to the drug product, all commercial batches should show similar dissolution profiles compared to the biobatch. This explains why it is recommended to set the Q value of the dissolution specification based on bio-batch dissolution results.
As dissolution profiles and f2 values are not determined routinely on commercial batches, these are irrelevant to the evaluation of the discriminatory power of the method. It is necessary that the dissolution profiles of the intentionally ‘mis-manufactured’ batches fail the proposed dissolution specification time point/s.
This article contains few steps you need to take to demonstrate the discriminatory power of a dissolution test method along with some examples.
Step 1: Identify and provide a list of critical attributes/parameters affecting the dissolution for your drug product.
Step 2: Compare the dissolution profiles of the drug product manufactured under target conditions versus the drug products that are intentionally manufactured with meaningful variations (i.e., formulations and manufacturing conditions) for the most relevant critical material attributes (CMAs), critical formulation variables (CMFs), and critical process parameters (CPPs) (e.g., drug substance particle size) (e.g., ± 10-20% change to the specified values or ranges for these variables) .
For Example:
1. You can submit data showing that the method can discriminate for meaningful changes in particle size distribution within the proposed specification ranges and outside these ranges.
2. Tablets that have been compressed to a higher compaction force and or excessive blending time can be used as samples which may exhibit a retarded drug release rate.
3. Increasing % of lubricant or binder, decreasing % of disintegrant may also exhibit a retarded drug release rate.
Read also: Guide to Determine Sink Conditions in Dissolution Testing
Resource Person: Pearl Pereira Nambiar
Post a Comment