Transdermal delivery of isoproterenol HCl: an investigation of stability, solubility, partition coefficient, and vehicle effects.
Effects of solubility, partition coefficient, and selected adjuvants (propylene glycol and Azone) on percutaneous penetration of isoproterenol HCl have been investigated using human cadaver skin. Isoproterenol was found to be stable (less than 1% decomposition) for 24 hr at 22 +/- 0.5 degrees C 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); however, decomposition was significant beyond pH 8. In normal saline, the rate of decomposition increased significantly with an increase in temperature to 37 degrees C. The solubility of isoproterenol HCl decreased and its skin/vehicle partition coefficient increased with increasing proportions of propylene glycol in the vehicle, while the product of the solubility and partition coefficient appeared to plateau at 20% propylene glycol in water. Optimal penetration enhancing effects of Azone were seen when incorporated at a concentration of 1% (v/v) in the 20% (v/v) propylene glycol-water blend and, more significantly, when skin was pretreated with pure Azone for 60 min prior to application of the drug formulation.
Patel
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School of Pharmacy, University of the Pacific, Stockton, California 95211.
Vasavada
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D001381:Azepines / Q000494:pharmacology; D004058:Diffusion; D004355:Drug Stability; D006801:Humans; D007545:Isoproterenol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014677:Pharmaceutical Vehicles; D012867:Skin / Q000378:metabolism*; D012995:Solubility
D001381:Azepines; D014677:Pharmaceutical Vehicles; C035229:laurocapram; D007545:Isoproterenol