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

Abstract 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.