NOVEL DOSAGE FORM TARGETING VAGINAL ADMINISTRATION

Currently, treatments for vaginal infections are mostly given orally or subcutaneously. However, because of extensive first-pass metabolism, the exposure of unchanged drug to the vaginal mucosa (i.e. bioavailability) after oral or subcutaneous dosing may be as low as 2.92%. Meanwhile, ointments for external application may result in pain or hypersensitivity. To address these problems, we proposed a novel composite dosage form consisting of polyurethane (PU) foam and aquagel impregnated therewithin. The PU/aquagel dosage form was shaped into a circular pad having diameter of about 5 cm, which made it suitable for being inserted into the vagina (average diameter 3 cm) thereby acting directly on cells within the inflamed lesion. We had successfully developed hydrophilic PU foam with an excellent water retention rate of about 1674%, which may retain 6.5-fold water as compared to convention PU foam. The hydrophilic PU foam comprised inter-connected cells which allowed the continuous flow of the aquagel along the struts, thereby allowing the aquagel to reach the peripheral of the PU foam and directly contact the lesion site. In this way, it is possible to deliver active compounds dispersed within the aquagel to the lesion site without enzymatic degradation. The active compounds would biologically adhere to the vaginal mucosa, thereby providing a fast-releasing yet sustained treatment. We investigated the relationship between the viscosity of the aquagel and the gel retention rate of the hydrophilic PU foam. Several over-the-counter medications for treating vaginal infections were dispersed in the aquagel, and in vitro transmembrane penetration analysis was conducted to elucidate the transmembrane delivery rate thereof. The O/W gel containing acyclovir exhibited a bioavailability of 60.7% at 26 h after the treatment, which is 19.4-fold compared to that of the orally administered acyclovir. This finding suggested that the novel dosage foam may reduce the concentration of active compounds, thereby reducing their cytotoxicity to normal cells.