A convolution-based in vitro-in vivo correlation model for methylphenidate hydrochloride delayed-release and extended-release capsule.

Abstract

Delayed-release and extended-release methylphenidate hydrochloride (JORNAY PM®) is a novel capsule formulation of methylphenidate hydrochloride, used to treat attention deficit hyperactivity disorder in patients 6 years and older. In this paper, we develop a Level A invitro-in vivo correlation (IVIVC) model for extended-release methylphenidate hydrochloride to support post-approval manufacturing changes by evaluating a point-to-point correlation between the fraction of drug dissolved invitro and the fraction of drug absorbed invivo. Dissolution data from an invitro study of three different release formulations: fast, medium, and slow, and pharmacokinetic data from two invivo studies were used to develop an IVIVC model using a convolution-based approach. The time-course of the drug concentration resulting from an arbitrary dose was considered as a function of the invivo drug absorption and the disposition and elimination processes defined by the unit impulse response function using the convolution integral. An IVIVC was incorporated in the model due to the temporal difference seen in the scatterplots of the estimated fraction of drug absorbed invivo and the fraction of drug dissolved invitro and Levy plots. Finally, the IVIVC model was subjected to evaluation of internal predictability. This IVIVC model can be used to predict invivo profiles for different invitro profiles of extended-release methylphenidate hydrochloride.