Date of Award


Document Type


Degree Name

Doctor of Philosophy (Ph.D.)



First Advisor

Ravindra C. Vasavada

First Committee Member

Madhukar G. Chaubal

Second Committee Member

Zak T. Chowhan

Third Committee Member

Hershel G. Frye

Fourth Committee Member

Marvin H. Malone


This research project was designed to test whether the in vitro percutaneous penetration of benzocaine through human cadaver skin could be enhanced by dimethyl sulfoxide (DMSO), urea, polyoxyethylene (20) isohexadecyl ether and 1-dodecylazacycloheptan-2-one (Azone) in propylene glycol/water systems. Solubility and partitioning of benzocaine in propylene glycol/water systems was investigated. The adjuvant effects were studied in a 60/40 (V/V) propylene glycol/water co-solvent system. The well known drug penetration enhancer dimethyl sulfoxide did not enhance the penetration of benzocaine at any concentration level of DMSO under the conditions of the experiment. This lack of enhancement effect was probably due to increased solubility of benzocaine in the DMSO/water system and a consequent decrease in the partitioning of drug into the skin. Urea enhanced benzocaine penetration initially but no significant steady-state penetration enhancement was noted. Polyoxyethylene (20) isohexadecyl ether appeared to retard rather than enhance the percutaneous penetration of benzocaine at concentrations below and around the critical micelle concentration. Azone showed concentration dependence for its enhancement effect on penetration of benzocaine. With 1% V/V Azone, the initial benzocaine penetration rate was higher compared to the other Azone concentrations. On the basis of comparative analysis of the steady-state rates, 5% V/V Azone was observed to be the most effective penetration enhancer for benzocaine. Azone also showed additive enhancement properties with increasing percentages of propylene glycol. The results of this investigation emphasize the importance of in vitro skin penetration studies prior to clinical evaluation. The results also underscore the importance of a proper experimental design that will minimize variables during the study in order to properly identify cause and effect relationships.





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