Development and validation of a discriminatory dissolution method for amorphous solid dispersion formulation of polymorphic Artemether

Abstract

The aim of this study was to develop and validate one discriminatory dissolution method for evaluation of amorphous solid dispersion of Artemether in its fixed dose combination (FDC) of Artemether lumefantrine tablets. Methods: The evaluation of discriminatory power of the selected dissolution method was based on saturation solubility and sink condition. The impact of addition of surfactant was evaluated in the selected dissolution method comparing the dissolution rate of Artemether from immediate release Artemether and lumefantrine tablets. Comparative dissolution profile of Artemether from conventional immediate release tablet and solid dispersion tablets were compared using the selected discriminatory dissolution method. The resulting final dissolution method was validated for linearity, precision, robustness and solution stability inline with ICH. Phosphate buffer pH 6.8 (without any surfactant) was finalized as the discriminatory dissolution method based on the comparative dissolution profile between conventional Artemether tablets and Artemether tablets prepared with solid dispersion technology. The proposed analytical method was capable to discriminate different formulation of Artemether .HPLC method with UV detection at wavelengths of 216 nm was followed.The method was found to be linear (R2=0.9998) over a range of 80-120 % of analyte target.The results for precision, robustness and solution stability were well within the acceptance limit for % RSD. The proposed dissolution method for amorphous solid dispersion of Artemether is robust and discriminatory which can be explored as a tool for quality control and also for in vivo assessment.