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Date of Award

1986

Document Type

Thesis - Pacific Access Restricted

Degree Name

Master of Science (M.S.)

Department

Graduate School

First Advisor

Ravindra Vasavada

First Committee Member

Marvin H. Malone

Second Committee Member

Patrick Catania

Abstract

This research utilizing full thickness human abdominal skin was designed to assess the in vitro percutaneous penetration of benzocaine by 1-dodecylazacycloheptan-2-one (Azone) , dimethylsulfoxide (DMSO) and 2-pyrrolidone (2-P) under conditions of constant thermodynamic activity in the vehicle. The solubilities of benzocaine in Azone and 80/20, 60/40 and 40/60 V/V DMSO/water systems were found to be 254.17, 533.00, 68.60 and 2.51 mg/ml respectively. All three adjuvants demonstrated a significant but concentration- dependent enhancement of benzocaine penetration. On the basis of comparative analysis of the steady-state fluxes, Azone was most effective at the level of 5% V/V when drug concentration was twice the saturation solubility _jn the 20/80 PG/water gel. At higher Azone levels, any penetration enhancement effects were strongly negated by a corresponding decrease in skin/vehicle partitioning. Azone appeared to enhance penetration of benzocaine molecules by directly reducing the barrier function of the stratum corneum. DMSO-induced enhancement of benzocaine penetration was observed over 40/80% V/V DMSO. Pretreatment studies strongly suggested that enhancement by DMSO is due to a significant but temporary effect on the epidermal barrier. The moderate enhancement of benzocaine penetration shown by 80% 2-P in water could be due to a decrease in diffusional resistance of stratum corneum brought on by a slow interaction between the stratum corneum and 2-P.

Pages

68

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