Novel Vaginal Controlled-Delivery Systems Incorporating Coprecipitates of Nonoxynol-9

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Abstract
The purpose of this study was to formulate Nonoxynol-9 (N-9) into a solid coprecipitate form which can be used in preparing pharmaceutically attractive and nonirritating vaginal controlled-release delivery systems (DDSs) such as gelatin capsules (HGC) and tablets. N-9 was coprecipitated with polyvinylpyrrolidone (PVP) with or without iodine to produce solid powders which were incorporated into either (a) bilayer tablet DDSs which possess a fast- (outer) and slow- (inner core) releasing compartment, and (b) HGC DDSs (named Triad HGC) composed of fast- (outer), intermediate- (granules), and slow- (pellets) releasing compartments. The rates of release of iodine and/or [14C]N-9 from the two DDSs were studied in vitro in phosphate buffer at pH 5.0, in human seminal plasma and in vivo after intravaginal administration in rabbits. In all of the above-described release studies, the DDSs were shown to release their N-9 or iodine content rapidly, reaching spermicidal levels within 3 min. This was further substantiated by experiments in which the DDSs were introduced in whole human semen containing live spermatozoa. Complete spermicidal kill was obtained in less than 1 min and in less than 3 min from the bilayer tablet and the Triad HGC, respectively. Furthermore, the release of N-9 from the two DDSs was shown to continue for at least 4 hr in buffers (pH 5.0), human seminal fluid, and after intravaginal administration in rabbits. The resulting powder from the coprecipitation of N-9 and PVP (K-30) can be appropriately formulated into a controlled-released HGC or bilayer tablet to produce vaginal controlled-release DDSs which are nonirritating and have the potential to become effective spermicidal products.