Discriminatory Dissolution Testing: a Quality by Design Approach for Formulation Development of Liquisolid Compacts Containing Poor Water Soluble Drug

Quality by design is a systematic approach to the product development that begins with pre-defined objectives and emphasizes on product and process understanding and control. The objective of this study was to develop a dissolution testing method for liquisolid compacts of clopidogrel which is capable of differentiating among the product with different formulation and/or processing parameters. In the present study, discriminatory dissolution method was developed and validated according to the USP and ICH guidelines. Solubility of clopidogrel in different dissolution media (HCl buffer, acetate buffer, phosphate buffer, purified water, and aqueous solution of Tween-80) was determined by flask shake method and optimum dissolution media was selected on the basis of sink conditions. USP apparatus and its speed were selected after thorough screening. Discriminatory power of the developed method was confirmed by determining dissolution profile of two formulations of liquisolid compacts, prepared with different load factor (0.25 and 0.5). On the basis of optimum solubility, non sink condition and consistent drug release, acetate buffer (pH 4.5) was selected as dissolution medium. Acetate buffer (1000 mL) stirred with USP apparatus-II (paddle) at 75 rpm were selected on the basis of optimum dissolution profile. Validated parameters were within the acceptable range (%RSD >2) and showed linearity (r2 = 0.999) in the range of 0-100 mu g/mL. Dissolution medium had no effect on clopidogrel analysis (peak purity approximate to 1) and dissolution samples remained stable for seven days. The developed dissolution method was able to discriminate beTween two liquisolid formulations prepared with different load factors and will help in formulation development and process.