Univariate and Multivariate Models for Determination of Prasugrel Base in the Formulation of Prasugrel Hydrochloride...

Prasugrel hydrochloride (PHCl) undergoes salt disproportionation, and the resulting prasugrel free base (PFB) may lead to the poor in vitro and or in vivo performance of the drug product. The aim of the present work was to develop univariate and multivariate models based on X-ray powder diffraction to quantify the salt and base in the powder and tablet formulations. Compositionally identical formulations of PHCl and PFB were prepared and mixed in various proportions to make 0%-30% PFB sample matrices. The formulations consisted of commonly used excipients, which are generally used in commercially available products. X-ray powder diffraction data were collected and subjected to the least square regression and partial least square regression analysis. The model performance parameters such as root mean squared and standard errors were low for univariate models compared to partial least square regression multivariate models. Model predicted values of the independent sample matrices by both methods matched closely with the actual values of PFB and PHCl. However, residual and standard deviation were low in univariate models predicted values. The models developed in this work have been shown to quantitate the PHCl disproportionation to PFB fraction in the drug product and provide a means to control the disproportionation of PHCl.