Abstract
A new in situ experimental method was designed to well predict and understand the muscle targeting and skin disposition of a topically applied drug. A disk shaped agar gel (3.85 cm in diameter and 0.5 cm in thickness) was firstly inserted between the hypodermis and the muscle layer in hairless rats. Flurbiprofen (FP), a model drug, was administered topically (using 3% HPC gel containing 1% drug) and intravenously into the rats. Drug disposition following topical application could be satisfactorily described by a pharmacokinetic model including cutaneous transport. The amounts of FP migrated from the formulation to the agar gel and the systemic circulation over 10 h were 12.4 and 1.92μg, respectively; namely most drug was absorbed into the systemic circulation. A ratio of FP into the agar gel from the formulation/the systemic circulation was found to 97.2/2.8. Moreover, the addition of several enhancers or vasoconstrictors affected a ratio of FP migration to the agar gel. This technique can be utilized as a new tool to evaluate the skin disposition of topically applied drugs.
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