A Comparative Study of the In Vitro and In Vivo Release of Dexamethasone from a Spray-On Bandage and Timed Release Aerosol

Abstract

The formulation of several dexamethasone topical delayed release aerosol preparations was studied. Ethylcellulose and tributyl citrate were the film-forming agent and plasticizer, respectively, for the spray-on bandage formulation. The aerosol timed release preparation contained dexamethasone microcapsules suspended in a fluorocarbon aerosol propellant by isopropyl myristate and fumed silica. Both preparations were evaluated using an in vitro method which measured the release of dexamethasone hourly for eight hours. In vitro studies showed that each of the formulations delayed the release of dexamethasone. In the in vivo tests aerosols were sprayed on the unabraded back area of rabbits and the increased 17 - hydroxycorticosteriod urine levels at 24, 48, and 72 hours indicated dexamethasone absorption. In vivo studies indicated that absorption did not occur with the timed release preparation containing dexamethasone microcapsules. However, dexamethasone from the spray-on bandage preparation was absorbed over 72 hours. A commercially marketed topical dexamethasone cream was used for comparison in evaluating the two experimental formulations; however, in vivo studies showed that no absorption occurred with this preparation.

In recent years, a great deal of work has been directed towards the application of medicated polymeric films or tissue adhesives onto the skin to treat minor dermatological problems or serious skin wounds. Among the factors to be considered are: incorporation of a specific active ingredient, the mode of application and the dosage form. Lange and Fang (1,2) developed spray-on bandages using water soluble resins and water as the solvent. Fischl (3) evaluated the effectiveness of a cyanoacrylate monomer in closing skin incisions without affecting wound healing. Bhaskar and Cutright (4) showed that butyl cyanoacrylate could be successfully used as a surface dressing while reducing the degree of inflammation. Sciarra and Gidwani (5,6) reported on the release of gentian violet from selected polymer and plasticizer combinations and established various polymer-plasticizer combinations which could be applied as an aerosol spray. Other studies (7,8) have shown that ethylcellulose and a thermoplastic polyamide resin have potential use in spray-on bandage formulations.

The results indicated that the anti-infectives were released from the films and the spray-on bandages reduced the degree of infection about the wound.

The process of microencapsulation has been applied to various industrial and medical uses. Microcapsules can be prepared so that the encapsulated material will be released slowly. There are various methods of microencapsulation including coacervation, phase separation, interfacial polymerization, an electrostatic method, and vacuum metalization and they have been successfully used with selected drugs (9-13).

The purpose of this study was to develop and evaluate different aerosol formulations containing a therapeutic agent which can be slowly released. In vitro and in Vivo systems were used to evaluate the release and absorption of the drug in the test animals.