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 in vitro-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 in vitro and the fraction of drug absorbed in vivo. Dissolution data from an in vitro study of three different release formulations: fast, medium, and slow, and pharmacokinetic data from two in vivo 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 in vivo 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 in vivo and the fraction of drug dissolved in vitro and Levy plots. Finally, the IVIVC model was subjected to evaluation of internal predictability. This IVIVC model can be used to predict in vivo profiles for different in vitro profiles of extended-release methylphenidate hydrochloride.