Biorelevant Dissolution Method Development for Dutasteride and Tamsulosin Hydrochloride Modified Release Capsule Simulating Post-prandial Condition

Abstract

Objectives: This research work is aimed to develop bio relevant dissolution method by simulating human gastrointestinal condition at post-prandial state. The quality control dissolution procedure for modified release product using simple buffers of specific pH is not adequate for prediction of in vivo performance. Methods: Percentage of drug absorbed is derived by deconvolution of drug plasma concentration at post-prandial condition using Wagner-Nelson deconvolution method. Quality control dissolution test is performed using office of generic drugs recommended dissolution method. Bio relevant dissolution method is developed using USP Apparatus 3 (reciprocating cylinder), with quality by design approach. A full factorial design of experiment study is performed for optimization of dips per minute and media volume. Separate dissolution method is developed for tamsulosin and dutasteride, since the formulation design and release profile are different for both drugs. Results: The dissolution profile obtained using quality control procedure is observed faster in comparison to percentage of drug absorbed. The bio relevant dissolution method developed for tamsulosin part is, 250ml of Fed state simulated change over dissolution media with 15DPM, based on desirability factor 0.8767 and for dutasteride part is, 100ml of pH 6.5 Fed state simulated intestinal fluid with 20DPM, based on desirability factor 0.5836, achieved from multiple response optimizations. The dissolution results are comparable to percentage of drug absorbed. The regression coefficient (R 2) value of 0.998 and 0.982 demonstrates a very good in vitro/in vivo correlation under post-prandial condition for tamsulosin and dutasteride respectively. Conclusion: The developed method shall be used as a predictive in vitro tool for evaluation of in vivo performance under post-prandial condition.