Microsealed Drug Delivery Systems I: In Vitro-In Vivo Correlation on Subcutaneous Release of Desoxycorticosterone Acetate and Prolonged Hypertensive Animal Model for Cardiovascular Studies

Abstract

A new generation drug delivery system, named the Microsealed Drug Delivery (MDD) system, was developed. Subcutaneous implantation of MDD’s in rats for up to 129 days resulted in a constant release profile of desoxycorticosterone acetate. Three formulations were examined. An excellent in vitro-in vivo correlation was established on both the mechanism and the rate of controlled release of desoxycorticosterone acetate from MDD’s. A significant degree of hypertension was reproducibly produced within 21 days after implantation and successfully sustained through Day 98. Comparative studies were conducted on MDD’s and a previously developed matrix-type silicone device. The elevation of systolic blood pressure initiated by either MDD’s or the matrix-type silicone device was essentially the same in pattern, and the difference in the hypertensive responses between these polymeric drug delivery systems was statistically insignificant, although a higher dose, which is time dependent, was administered to rats through the matrixtype silicone device than through MDD’s. The bioavailability of desoxycorticosterone acetate and its dose-response relationship apparently were accomplished more effectively via the constant drug delivery mechanism of MDD’s.