Disintegration and dissolution testing is often seen as in-process/release control step, not relevant from the perspective of product bio-performance. The aim of this paper was to develop discriminative and bio-relevant (Fasting conditions) disintegration and dissolution methods for an immediate release generic tablet with poorly soluble BCS 4 drug substance with known wetting issues and tendency to aggregate. Tablet with atypically long disintegration, similar to reference product, had to be developed. Several non-standard disintegration methods were designed and those simulating no mechanical stress and fasting gastric environment were found to correlate best with in vivo result. To assure fast high-throughput screening of samples for developmental purposes, conditions identified in disintegration tests were incorporated into custom made dissolution test that covers both disintegration and drug release while simulating bio-relevant fasting conditions. With all available data we were able to correlate in vitro data to the in vivo result and identify critical parameters responsible for product bio-performance.
Published Date: 2021-12-27; Received Date: 2021-12-06