Thiomenthol Derivatives as Novel Percutaneous Absorption Enhancers
| Autor: | Kozo Takayama, Yuki Takanashi, Hideaki Komiya, Kimio Higashiyama, Tsuneji Nagai |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Ketoprofen Stereochemistry Chemistry Pharmaceutical Skin Absorption Pharmaceutical Science Absorption (skin) Administration Cutaneous medicine.disease_cause Dosage form Structure-Activity Relationship Pharmacokinetics Drug Discovery medicine Animals Rats Wistar Skin Pharmacology Chromatography biology Chemistry Organic Chemistry Hydrogels Rats Partition coefficient Menthol Solubility Enzyme inhibitor Self-healing hydrogels biology.protein Regression Analysis Irritation Software medicine.drug |
| Zdroj: | Drug Development and Industrial Pharmacy. 25:89-94 |
| ISSN: | 1520-5762 0363-9045 |
| DOI: | 10.1081/ddc-100102146 |
| Popis: | Thiomenthol derivatives were synthesized and their promoting activity on the percutaneous absorption of ketoprofen from hydrogels was evaluated in rats. The apparent penetration rate (Rp) of ketoprofen absorbed from the hydrogel was estimated by the pharmacokinetic model derived under the assumption of a constant penetration rate through the skin after a lag time. As an index of promoting activity of thiomenthol derivatives, an enhancement factor (Ef) was defined as the ratio of the Rp value with enhancer to the value obtained with the control not containing enhancer. Skin irritancy evoked by these derivatives was investigated microscopically by using a cross-section of the excised skin onto which ketoprofen hydrogel was applied. Total irritation score (TIS) was estimated by summation of each irritation score in several parts of the skin. The physicochemical parameters of thiomenthol derivatives such as a partition coefficient (log P) and a steric energy were calculated and the quantitative relationships between these parameters and the Ef values or TIS values were investigated on the basis of multiple regression analysis. As a result, a parabolic relationship between log P and Ef was noted. A similar relationship was also observed in the case of TIS. |
| Databáze: | OpenAIRE |
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