Development and evaluation of a dexamethasone timed-release aerosol formulation.

Dexamethasone microcapcules were prepared and in vitro parameters were determined by sieve analysis which yielded materials retained on Nos. 80-, 100-, 200-, and 270-mesh sieves. Release rate and direct total determinations indicated that some measure of timed release appeared in all four sieve samples. The pH-release rate profiles of the microcapsules indicated that dissoution was pH independent. Colloidal silica and isopropyl myristate formulations provided the best suspending characteristics of all aerosol formulations evaluated. Delivery rate, pressure, and evacuation testing demonstrated the usability and functionality of the aerosol. An evaluation was made on the effect on urinary excretion levels of 17-hydroxycorticosteroid when a physical admixture of the drug and timed-release microcapsules were sprayed on rabbits. The significantly higher 17-hydroxycorticosteroid levels obtained in urine of animals treated with the admixture after 1 day may have been attributed to both an immediate suppression of the endogenous steroid and the "spilling over" of excess dexamethasone. A significant difference also was found at the 90% confidence level among the 24, 48, and 72-hr 17-hydroxycorticosteroid levels in the admixture and the microcapsules, which substantiated the delayed effect of the latter.