I have developed a sustained release tablet of a BCS class III molecule (highly soluble in acidic media) with POLYOX™ WSR N60K and Polyethylene Glycol 6000. I am getting less than 90% in every manufacturing process (top spray granulation, roller compaction, and hand granulation). However, when I formulate the tablet with HPMC instead of using POLYOX™ WSR N60K and Polyethylene Glycol 6000, I get an assay result of about 99%. The assay is conducted by the HPLC method. Buffer is prepared by Potassium Dihydrogen Phosphate at pH 2.5 ± 0.05. Diluent prepared by using buffer solution and methanol at a ratio of 90:10% v/v.

Test sample preparation method: Randomly select 20 tablets and take the average weight. Accurately weight and transfer 10 tablets into a 500 mL volumetric flask. Add 200 mL of Acetonitrile and sonicate the sample to disintegrate for 60 minutes (or up to disintegration occurs) with intermittent shaking to dissolve well. Keep the solution at room temperature and make the volume up to the mark with diluent. mix it well. Transfer 5 mL of this solution into a 100 mL volumetric flask and make the volume up to the mark with diluent and mix it well. Please suggest me how I can fix the problem and get a satisfactory release of the tablet.