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

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 vivo experimentation using a female Sprague-Dawley rat model confirmed the successful delivery of OLP from hydrogel-forming MAPs (C_max = 611.13 ± 153.34 ng/mL, T_max = 2 h) and dissolving MAPs (C_max = 690.56 ± 161.33 ng/mL, T_max = 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 OLP via the 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.

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Materials

The following materials were used in the study: OLP (Tokyo Chemical Industry, Zwijndrecht, Belgium); Gantrez S-97 (a copolymer of methyl vinyl ether and maleic acid), PVP (58 and 360 kDa, sold under the product brand names Plasdone K-29/32 and K-90), and β-CD, HP-β-CD, γ-CD, and HP-γ-CD (sold under the product brand names of Cavamax W7, Cavitron W7, Cavamax W8, and Cavasol W8, respectively, Ashland, Vale Industrial Estate, Kidderminster, U.K.); sorbitol, poly(ethylene glycol) (PEG, MW 3400 and 10,000 Da), poly(vinyl alcohol) (PVA, MW 85–124 kDa, 87–89% hydrolyzed), PVA (MW 9–10 kDa, 80% hydrolyzed), and d-α-tocopherol poly(ethylene glycol) 1000 succinate (TPGS, Sigma-Aldrich, Steinheim, Germany); crospovidone (CPV, sold under the product brand name Kollidon CL-SF, O-BASF, Ludwigshafen, Germany); anhydrous citric acid, anhydrous glucose, and anhydrous sodium carbonate (Na2CO3) (BDH Laboratory Supplies, Poole, Dorset, England); Parafilm M laboratory film (Bemis Company Inc., Soignies, Belgium); siliconized release liner (Rexam Release B.V., Apeldoom, The Netherlands); pluronic F-108 (VWR Chemicals LLC, Solon, OH); poly(lactic acid) (PLA) (Ultimaker, Geldermalsen, Netherlands); Kinesiology Sports tape (95% cotton, 5% spandex; 5 × 500 cm; Proworks Corporation, Corvallis, OR); and microfoam surgical tape and Tegaderm dressing (3 M, Bracknell, Berkshire, U.K.).

Peter E. McKenna, Marco T. A. Abbate, Lalit K. Vora, Akmal H. Sabri, Ke Peng, Fabiana Volpe-Zanutto, Ismaiel A. Tekko, Andi Dian Permana, Cian Maguire, David Dineen, Mary-Carmel Kearney, Eneko Larrañeta, Alejandro J. Paredes, and Ryan F. Donnelly, Polymeric Microarray Patches for Enhanced Transdermal Delivery of the Poorly Soluble Drug Olanzapine, Cite This: https://doi.org/10.1021/acsami.3c05553

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