An investigation of in vitro percutaneous penetration enhancement of benzocaine by azone, dimethylsulfoxide, and 2-pyrrolidone

• Main Author: Benkorah, Amal Y.
• Format: Others
• Published: Scholarly Commons 1986
• Subjects: Drug carriers (Pharmacy); Skin absorption; Dermatologic agents; Medicine and Health Sciences
• Online Access: https://scholarlycommons.pacific.edu/uop_etds/494; https://scholarlycommons.pacific.edu/cgi/viewcontent.cgi?article=1493&context=uop_etds

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.