Formulation optimization of indomethacin gels containing a combination of three kinds of cyclic monoterpenes as percutaneous penetration enhancers
| Autor: | Karin Kragh Levison, Kozo Takayama, Koichi Isowa, Tsuneji Nagai, Keiichiro Okabe |
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| Rok vydání: | 1994 |
| Předmět: |
Male
Stereochemistry Administration Topical Skin Absorption Indomethacin Pharmaceutical Science Absorption (skin) Dosage form Excipients chemistry.chemical_compound In vivo Linear regression Animals Response surface methodology Rats Wistar Confidence region Chromatography Ethanol Chemistry Terpenes Regression analysis Rats Propylene Glycols Injections Intravenous Regression Analysis Menthol Gels |
| Zdroj: | Journal of pharmaceutical sciences. 83(9) |
| ISSN: | 0022-3549 |
| Popis: | A computer optimization technique based on response surface methodology was applied for the optimization of a hydrogel formulation containing indomethacin as a model drug. As the penetration enhancer, a combination of three cyclic monoterpenes, limonene, menthol, and cineole, was employed. Pharmacokinetic parameters, from an in vivo percutaneous absorption study on rats of model formulations prepared according to the composite experimental design for five factors, were determined as prime response variables. The skin damage evoked by each formulation was microscopically judged and graded as the response variable concerning skin safety. The response variables were predicted by multiple regression equations comprising combinations of the five formulation factors. The regression equations for the response variables assembled as a simultaneous optimization problem based on the generalized distance function. The simultaneous optimum was predicted as a function of individual optima within a 95% confidence region. The predicted response values for the optimum formulation have been successfully validated in a repeated in vivo percutaneous absorption study. |
| Databáze: | OpenAIRE |
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