Vaginal pessaries from crystalline/rubbery hydrogels for the delivery of prostaglandin E2

Abstract The preparation of storage-stable controlled release devices for prostaglandin E 2 (PGE 2 ) is described. A semi-crystalline hydrogel of crosslinked poly(ethylene oxide) was swollen with a solution of PGE 2 in an organic solvent at room temperature, thus avoiding contact with water or heat, both of which degrade the PGE 2 . The greater organic solubility allowed PGE 2 to be introduced into the polymer matrix in excess of its water solubility. By using a simple slab form with a variable thickness for the device, the in vitro half life of prostaglandin in the hydrogel could be predicted. Uniform release for approximately the half life into an aqueous release medium can be achieved from the dried devices. Hypotheses are proposed to explain the mechanism of PGE 2 release from the swelling hydrogel using the data of release profiles for different thicknesses, loadings and compositions of polymer. As well as laboratory preparations, more than 400 pessaries have been prepared for clinical evaluation in ripening the cervix and inducing labour. Laboratory pessaries have been stored at 4°C for more than a year with no significant change in the release profile nor degradation of PGE 2 .