Transdermal patches for D-threo-methylphenidate (free base): Formulation aspects and in vivo pharmacokinetics

This study was designed to develop a drug-in-adhesive (DIA) type transdermal drug delivery system (TDDS) for D-threo-methylphenidate (D-threo-MP) that could be further developed for treating Attention-Deficit/Hyperactivity Disorder (ADHD) in children. During initial formulation optimization, three formulation factors, i.e., different adhesives, permeation enhancers and drug loading of D-threo-MP were screened using vertical Franz diffusion cells across newborn pig skin. A patch containing 15% (w/w) D-threo-MP in DURO-TAK®87-4098 was considered as an optimum patch which was selected for in vivo studies. The optimum D-threo-MP patch pharmacokinetic parameters were determined in Sprague Dawley (SD) rats and bama miniature pigs (Sus scrofa domestica) after application of transdermal patches, intravenous (i.v.) injection or oral administration. The absolute bioavailability and the relative bioavailability of D-threo-MP DIA patch in the SD rats model were 53.4% and 218.8%, respectively, and the relative bioavailability was 83.4% in the bama miniature pigs model. In this study, we showed that the optimized D-threo-MP patches could be further developed for treating Attention-Deficit/Hyperactivity Disorder (ADHD) in children.

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