Polymeric Microarray Patches for Enhanced Transdermal Delivery of the Poorly Soluble Drug Olanzapine

Transdermal drug delivery is an alternative route ofadministrationthat offers avoidance of the associated drawbacks of orally and parenterallyadministered hydrophobics. However, owing to the extremely specificset of physicochemical characteristics required for passive transdermaldrug permeation, the development of marketed transdermal productscontaining poorly soluble drugs has been severely limited. Microarraypatches (MAPs) are a type of transdermal patch that differ from thetraditional patch design due to the presence of tiny, micron-sizedneedles that permit enhanced drug permeation on their applicationsurface. To date, MAPs have predominantly been used to deliver hydrophiliccompounds. However, this work challenges this trend and focuses onthe use of MAPs, in combination with commonly utilized solubility-enhancingtechniques, to deliver the hydrophobic drug olanzapine (OLP) acrossthe skin. Specifically, cyclodextrin (CD) complexation and particlesize reduction were employed in tandem with hydrogel-forming and dissolvingMAPs, respectively. In vivo experimentation usinga female Sprague-Dawley rat model confirmed the successful deliveryof OLP from hydrogel-forming MAPs (C (max) = 611.13 & PLUSMN; 153.34 ng/mL, T (max) =2 h) and dissolving MAPs (C (max) = 690.56 & PLUSMN; 161.33 ng/mL, T (max) = 2 h) in amanner similar to that of oral therapy in terms of the rate and extentof drug absorption, as well as overall drug exposure and bioavailability.This work is the first reported use of polymeric MAPs in combinationwith the solubility-enhancing techniques of CD complexation and particlesize reduction to successfully deliver the poorly soluble drug OLP via the transdermal route. Accordingly, this paper providessignificant evidence to support an expansion of the library of moleculesamenable to MAP-mediated drug delivery to include those that exhibitpoor aqueous solubility.