Progestin permeation through polymer membrane V: Progesterone release from monolithic hydrogel devices.

Progesterone release from monolithic devices prepared from various copolymers of poly(hydroxyethyl methacrylate) and poly(methoxyethoxyethyl methacrylate) or poly(methoxyethyl methacrylate) was examined. In general, plots of the fraction of drug released versus (time)1/2 were linear during the early stages of drug release. This behavior is similar to that found for drugs released from hydrophobic polymers such as polydimethyl siloxane. However, for some release curves using the hydrogels, a breakpoint appeared during the early stages of drug release. These breakpoints were due to the effects of water absorption by these polymers. From analyses of permeability coefficients, it was demonstrated that release rates also were dependent on the initial drug load and the equilibrium water content of the polymer. These conclusions were verified from cross-membrane diffusion studies on films depleted of their initial drug load. In conjunction with this work, the aqueous solubility of progesterone was determined by several methods; an average value of 38 micrograms/ml at 23 degrees was obtained.