ORIGINAL ARTICLE Design of transdermal matrix patch containing ondansetron Jeong-Rae Cho 1 • An Van Duong 2 • Linh Thi Thao Nguyen 2 • Sang-Cheol Chi 2 Received: 13 July 2016 / Accepted: 9 August 2016 / Published online: 18 August 2016 Ó The Korean Society of Pharmaceutical Sciences and Technology 2016 Abstract Ondansetron was formulated into a transdermal matrix patch to reduce side effects and improve patient compliance. The effects of adhesive (polyisobutylene rubber, acrylic, and styrene butadiene rubber), crosslinker content (aluminum), vehicle (lactic acid), and drug amount on ondansetron skin permeation rate were investigated using excised hairless mouse skin with a flow-through diffusion cell system. Acrylic adhesive resulted in a higher ondansetron permeation rate than that of other adhesives. The ondansetron matrix patch prepared with acrylic adhe- sive without the crosslinker showed the highest permeation rate of 0.92 lg/cm 2 /h. Adding the crosslinker to the matrix patch reduced ondansetron skin permeation rate. The molecular weight and functional group of adhesive did not affect skin permeation of ondansetron from the matrix patch. As the amount of ondansetron in the matrix patch was increased (2.0–6.5 %), skin permeation rate increased up to 5 % of the drug, which was unchanged beyond this concentration. Based on these results, the optimum for- mulation for an ondansetron matrix patch consisted of 5 % ondansetron, 5 % lactic acid, 19.9 % N-methyl-2-pyrroli- done, 5 % ethyl oleate, 2 % glycerol monooleate, and 63.1 % acrylic adhesive (SK 1570-50F). This optimized matrix patch resulted in a skin permeation rate of 1.01 ± 0.21 lg/cm 2 /h through excised hairless mouse skin. Keywords Ondansetron Á Transdermal Á Adhesive Á Patch Introduction Ondansetron is the first selective 5-HT 3 antagonist used to relieve and prevent nausea and emesis induced by chemotherapy and radiotherapy (Butcher 1993; Roila et al. 1993). It has been proven efficient and safe to treat such symptoms (Christofaki and Papaioannou 2014). The drug is administered orally and intravenously for emetogenic anti-cancer drugs at recommended oral dose of 8 mg three times daily. Transdermal formulations of ondansetron have been considered to reduce dosing frequency, side effects, and improve patient compliance. Ondansetron has a relatively short elimination half-life (3–6 h) and low bioavailability (60 %) (Denge et al. 2012). Ondansetron is a good candidate for a transdermal delivery system (Gwak et al. 2003; Rajabalaya et al. 2013) due to its low molecular weight (293.36 g/mol), good efficacy at low dose, a log P value of 2.07, and good permeability of 2.81 ± 2.56 lg/cm 2 /h (Prausnitz and Langer 2008; Subedi et al. 2010; Denge et al. 2012; Can et al. 2013). Transdermal formulations have several advantages, such as avoiding the first-pass effect of the drug and maintaining a therapeutic steady-state plasma concentration of the drug from a single dose (Prausnitz and Langer 2008; Jhawat et al. 2013). The effect of some esters, alcohols, ethers, fatty acids, and fatty alcohols on in vitro permeation of ondansetron through excised hairless mouse skin has been investigated to screen vehicles and enhancers for transdermal delivery of ondansetron (Gwak et al. 2004). Ondansetron permeation through a membrane using transdermal patch prepared from chitosan, hydroxypropyl- methylcellulose, and Eudragit RL 100 has also been studied & Sang-Cheol Chi scchi@gachon.ac.kr 1 WooSung Pharma. Inc., 121 Seocheon-ro, Giheung-gu, Yongin-si, Gyeonggi-do, South Korea 2 College of Pharmacy, Gachon University, 191 Hambakmoeiro, Yeonsu-gu, Incheon 406-799, South Korea 123 Journal of Pharmaceutical Investigation (2016) 46:677–684 Online ISSN 2093-6214 DOI 10.1007/s40005-016-0273-9 Print ISSN 2093-5552