Biorelevant Dissolution Method Development For Dutasteride/Tamsulosin Hydrochloride Modified Release Capsule - A Prognostic Tool For Oral Drug Absorption

Abstract

The research work was aimed to develop a biorelevant dissolution method for fixed dose combination containing Dutasteride 0.5 mg in immediate-release form and Tamsulosin 0.4 mg in modified-release form. Mean plasma concentration achieved after oral administration to human under pre-prandial condition are deconvoluted using Wagner-Nelson deconvolution method, to achieve target dissolution profile. The dissolution profile observed using office of generic drugs recommended dissolution media was observed to be faster than the target dissolution profile. Tamsulosin being a modified-release multiparticulate system, biorelevant dissolution method was developed with Fasted state simulated change over dissolution media, using USP Apparatus 3 (reciprocating cylinder). Dutasteride being an immediate-release form, dissolution method was developed with single dissolution media, by extending the dissolution run time upto C max . Dissolution media, media volume and Dips Per Minute (DPM) are optimized by performing full factorial design of experiment. The ANOVA result interprets the biorelevant dissolution media for Tamsulosin part is 250 ml of Fasted state simulated change over dissolution media with 15 DPM, based on desirability factor of 0.7768 and for Dutasteride part 250 ml of pH 6.5 Fasted state simulated intestinal fluids with 7 DPM, based on desirability factor of 0.8988. The regression co-efficient (R 2 ) value of 0.999 and 0.996 demonstrates a very good in-vitro/in-vivo correlation under pre-prandial condition for Tamsulosin and Dutasteride respectively. The developed method shall be used as a predictive in-vitro tool for evaluation of in-vivo performance under pre-prandial condition.