The Use of Experimental Design Principles in Dissolution Method Development: Development of a Discriminating Dissolution Method for Sprycel Film-Coated Tablets

Sprycel® (dasatinib) film-coated tablet is a new medicinal product that was recently launched for the treatment of chronic myelogenous leukemia. Due to the early success of dasatinib in phase I clinical trials, development activities were accelerated significantly to enable wide distribution of this drug to patients. As a BCS class II compound, dissolution was considered a critical quality attribute of dasatinib film-coated tablets and a discriminating dissolution method was required to support tablets intended for Phase II clinical trials and commercial use. A systematic experimental approach was established to rapidly screen media pH, solubility enhancers, and concentration in order to overcome the challenges of a tight timeline and limited study materials. The final validated method utilizes 1,000 mL of pH 4.0 acetate buffer with 1% Triton X-100 with a USP Apparatus II (paddle) rotating at 60 rpm and a HPLC sample analysis.