Dissolution Profiling for Generic Solid Dosage form

Question

We are doing Hydroxychloroquine Sulfate 200 mg tablet Dissolution profile V/s Plaquenil 200 mg Tablet. The drug has very high solubility ratio.We start profiling with 500 ml volume, Apparatus II,50 RPM,37 degree in Buffer: pH 1.0 &ndash; 1.2 (usually 0.1 N HCl or SGF without enzymes), pH 4.5, and pH 6.8. In pH4.5 and 6.8 buffers we achieved dissolution >85% within 15 min. In pH 1.2 for generic formulation dissolution not achieved >85% within 15 min although innovator found okay. So i would like here guidance for how to proceed further. Should i go for increased volume of 750 ml or 900 ml only for pH 1.2 buffer with 75 RPM with both Test and innovator. Can anyone guide me in such cases, how to proceed for this as this study is needed for biowaiver. I need to understand practical way to overcome this issue with regulatory compliance also. 
 Please need guidance for me. 
 
 Regards 
 
 Nandkumar

kenboda · Answer

Generally, you would start method development with what you find in the USP and/or FDA Dissolution Method Databases for volume, media, RPM, etc. requirements. The FDA method database points you to: Dissolution Testing and Acceptance Criteria for Immediate-Release Solid Oral Dosage Form Drug Products Containing High Solubility Drug Substances Guidance for Industry (fda.gov) The preference is for 500mL for highly soluble drugs, but higher volumes, etc. can be done with proper justification and testing. The USP indicates 900mL of water is to be used: Resources - Dissolution Methods Database: | USP 
 If you're just looking for the acid media as part of a multimedia study, then you might be asked to evaluate a higher media volume and also looking at more time points 15, 20, 30, 45, and 60 minutes being common other time points.

Dissolution Profiling for Generic Solid Dosage form

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