In vitro and in vivo considerations of a novel matrix-controlled bovine progesterone-releasing intravaginal device

An in vitro system measuring progesterone release from silicone matrixes into serum is described. Drug release followed a matrix-controlled diffusion model in which the cumulative quantity released was linear with the square root of time. A bovine intravaginal device, consisting of a steel coil coated on both sides with a progesterone silicone matrix, was used as an in vivo drug delivery system. In vivo drug release also was matrix controlled, with rates comparable to those obtained in vitro. However, lag times of 1.7 and 4.2 days before reaching the steady-state rate were obtained for the outer and inner surfaces, respectively. The combination of effects resulted in a pseudo-zero-order drug-releasing device in which cumulative drug released was linear with time for at least 16 days.