A statistical approach to the development of a transdermal delivery system for ondansetron.
Transdermal delivery of drugs has gained attention as an alternative to intravenous and oral methods of delivery. However, the skin permeation of drugs is generally poor. To overcome this problem, many permeation enhancers have been developed. In this study, ondansetron hydrogels were prepared, and their skin permeation and pharmacological effects were evaluated in mice. To prepare the hydrogels, a Box-Behnken design was introduced. Fifteen formulations of ondansetron hydrogels composed of hydroxyethylcellulose and hydroxypropylcellulose as gel bases, l-menthol as a penetration enhancer and isopropanol (IPA), N-methyl-2-pyrrolidone (NMP) and water as a solvent were prepared. The quantities of IPA (X(1)), l-menthol (X(2)) and NMP (X(3)) were selected as causal factors. We performed an in vitro skin permeation study and an in vivo skin irritation study with the test hydrogels. The flux and the total irritation score were selected as response variables. The optimal formulation, one that has an appropriate penetration and an acceptable skin irritation score, was estimated using a nonlinear response surface method incorporating thin-plate spline interpolation. The optimal formulation also delivered the desired pharmacological activity. These results indicated the feasibility of delivering ondansetron transdermally.
Obata
Yasuko
Y
Department of Pharmaceutics, Hoshi University, Tokyo, Japan. obata@hoshi.ac.jp
Ashitaka
Yuriko
Y
Kikuchi
Shingo
S
Isowa
Koichi
K
Takayama
Kozo
K
D000279:Administration, Cutaneous; D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000706:statistics & numerical data; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000706:statistics & numerical data*; D016503:Drug Delivery Systems / Q000379:methods*; D004435:Eating / Q000187:drug effects; D020100:Hydrogels; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D017294:Ondansetron / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D023422:Skin Irritancy Tests
D000932:Antiemetics; D004337:Drug Carriers; D020100:Hydrogels; D017294:Ondansetron