Transport of prostaglandins through silicone rubber

The in vitro release profiles of the F-series of prostaglandins were determined from a silicone rubber matrix of constant surface area. Silicone rubber was selective toward prostaglandin transport and offers potential as a controlled-release delivery system. Drug release patterns were dependent on the lipophilicity of the prostaglandin molecule. For dinoprost (prostaglandin F2 alpha), the following sequences was observed: methyl ester greater than free acid greater than tromethamine salt. The biologically potent carboprost methyl [(15S)-15-methylprostaglandin F2 alpha methyl ester] was release considerably faster than the methyl ester of the parent dinoprost molecule, while release of the tromethamine salt of the two prostaglandins was similar. Permeability rates of the salts were depressed substantially when compared to their respective C-1 methyl esters. Results from independent membrane transport studies supported the observed dependence of steady-state flux on the chemical structure of the prostaglandin molecule. Plots of the amount released per unit area versus the square root of time were linear except for the initial drug release phase, and the total amount of prostaglandin released increased as the initial loading dose was raised. The data were analyzed according to a physical model describing drug release from inert matrix systems. The observed concentration dependence was consistent with the predictions of the model.