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Date of Award


Document Type


Degree Name

Doctor of Philosophy (Ph.D.)



First Advisor

Ravindra Vasavada

First Committee Member

Madhukar Chaubal

Second Committee Member

Marvin H. Malone

Third Committee Member

Donald Y. Barker

Fourth Committee Member

Herschel Frye


Effects of solubility, partition coefficient, pH and selected adjuvants (propylene glycol and Azone) on the percutaneous penetration of isoproterenol HC1 in vitro have been investigated using human cadaver skin. Preliminary stability studies demonstrated that isoproterenol HC1 was very stable (less than 1% decomposition) for 24 hours at 22(DEGREES) (+OR-) 0.5(DEGREES) in the pH range 1 to 7 in the following solvents: water, normal saline, propylene glycol and a series of propylene glycol-water mixtures (10,20,40 and 60% v/v). The rate of decomposition of the drug in aqueous solutions increased with pH beyond pH 8. In normal saline, the decomposition was significant when the temperature was raised to 37(DEGREES) (+OR-) 0.5(DEGREES). The solubility of isoproterenol HC1 decreased and its skin/vehicle partition coefficient increased with increasing proportions of propylene glycol in the vehicle. Results of the physicochemical and percutaneous penetration studies revealed that 20% v/v propylene glycol in water should be the optimal vehicle for transdermal delivery of isoproterenol HC1. Optimal penetration enhancing effects of AzoneR were seen when incorporated at a concentration of 1% v/v in the 20% v/v propylene glycol-water vehicle and more dramatically when the skin was pretreated with pure Azone for 60 minutes prior to application of the drug formulation. The flux reached a maximum around pH 9 in agreement with the predicted favorable pH environment for neutral forms of isoproterenol HC1. Both neutral and charged forms of isoproterenol HC1 were found to contribute to the total flux in agreement with the proposed model: J = ( Kp . C )ca + ( Kp . C )an + ( Kp . C )n. The calculated permeability coefficients for isoproterenol HC1 were 0.2098 x 10-3, 0.1570 x 10-4 and -0.8665 x 10-3 cm/h for neutral, cationic and anionic species, respectively. Azone enhanced the penetration of all forms of isoproterenol HC1, although the effect was more pronounced on the anionic species. This may be due to facilitation of penetration by formation of an ion-pair between isoproterenol HC1 and Azone. The permeability coefficients for the neutral, cationic and anionic forms of isoproterenol HC1 for penetration through Azone-pretreated skin were 0.8395 x 10-3, 0.1701 x 10-3 and 0.8091 x 10-2 cm/h, respectively.