This morning I received the following query (my response is included below) about the manufacturing aspect of the above-mentioned drug product. It is hoped that authorities will take note and address the issue faced by the industry to manufacture this essential pharmaceutical product as per my year-and-a-half-old Citizen Petition (link).
Query:
“Regarding the dissolution of HYDROXYCHLOROQUINE SULPHATE TABLETS, the disso medium specified in IP & USP is water. The formulation sometimes fail to conform to IP and even USP parameters
I have tried replacing water with 0.1 M hydrochloric acid as dissolution medium and achieved a disso of above 90 %. I know the api is water soluble, but since this is an instant release formulation and the approximate pH of stomach is being maintained in disso medium, can we recommend change of disso medium from water to 0.1 M H Cl to IP & USP.
Response:
Scientifically speaking, water is a suitable dissolution medium, not the HCl (link).
In reality, your suggestion of changing the medium from water to HCl is for obtaining desired dissolution results, which is neither scientific nor logical.
In general, the issue you are describing is not of medium choice but the choice of the dissolution apparatus. USP apparatuses are known to provide slower and irrelevant results; most likely, you are observing this flaw. Such an issue can only be addressed by changing the tester, not the medium, rpm, etc. Considering USP apparatuses’ flaws and limitations, I have proposed a new stirrer to address this issue. Perhaps consider using this suggested spindle and simpler dissolution method not only for this product but also to avoid future issues with USP apparatuses. Additionally, there is a stronger argument for using an alternate dissolution tester than changing the dissolution medium, i.e., the USP apparatuses are non-GMP compliant (link, link).
I hope you will find the suggestion useful, and best of luck.
PS: Please request the authorities, in particular FDA and USP, to withdraw the requirement of using non-GMP (i.e., non-validated/non-qualified testers/methods) and allow the use of scientifically valid testers and methods to develop and manufacture urgently needed pharmaceutical products.