Transdermal drug delivery is an alternative route of
administration
that offers avoidance of the associated drawbacks of orally and parenterally
administered hydrophobics. However, owing to the extremely specific
set of physicochemical characteristics required for passive transdermal
drug permeation, the development of marketed transdermal products
containing poorly soluble drugs has been severely limited. Microarray
patches (MAPs) are a type of transdermal patch that differ from the
traditional patch design due to the presence of tiny, micron-sized
needles that permit enhanced drug permeation on their application
surface. To date, MAPs have predominantly been used to deliver hydrophilic
compounds. However, this work challenges this trend and focuses on
the use of MAPs, in combination with commonly utilized solubility-enhancing
techniques, to deliver the hydrophobic drug olanzapine (OLP) across
the skin. Specifically, cyclodextrin (CD) complexation and particle
size reduction were employed in tandem with hydrogel-forming and dissolving
MAPs, respectively.In vivoexperimentation using
a female Sprague-Dawley rat model confirmed the successful delivery
of OLP from hydrogel-forming MAPs (Cmax= 611.13 ± 153.34 ng/mL,Tmax=
2 h) and dissolving MAPs (Cmax= 690.56
± 161.33 ng/mL,Tmax= 2 h) in a
manner similar to that of oral therapy in terms of the rate and extent
of drug absorption, as well as overall drug exposure and bioavailability.
This work is the first reported use of polymeric MAPs in combination
with the solubility-enhancing techniques of CD complexation and particle
size reduction to successfully deliver the poorly soluble drug OLPviathe transdermal route. Accordingly, this paper provides
significant evidence to support an expansion of the library of molecules
amenable to MAP-mediated drug delivery to include those that exhibit
poor aqueous solubility.