Comparison of a poloxamer-based thermally sensitive gel and an HPMC-based standard gel used to increase sildenafil citrate retention in the uterus.

OBJECTIVE

Sildenafil citrate (SC) could promote uterine lining development, leading to successful embryo implantation. Due to the low oral bioavailability of the first-pass elimination of SC, it is necessary to develop a gel for vaginal administration to improve the efficacy.

METHODS

A vaginal gel was prepared using the cold method to increase the retention of SC in the uterus, which allows for prolonged contact between SC and the vaginal mucosa. A poloxamer-based thermosensitive in situ gel containing SC (SC-Tsgel) and an HPMC-based standard gel containing SC (SC-Cogel) were prepared. The rheological properties, in vitro drug release, and in vivo retention in the uterus of SC-Tsgel and SC-Cogel were compared.

RESULTS

The gel formulations significantly prolonged the time it took for drugs to be released following a release study. SC-Tsgel and SC-Cogel administered vaginally increased the duration of drug administration compared to SC solutions injected through the tail vein. Nevertheless, compared with tail vein injection of SC solutions or vaginal administration of the SC-Cogel, the retention of SC in the uterus was increased significantly after vaginal administration of the SC-Tsgel.

CONCLUSIONS

Novel formulations of SC prepared with poloxamer 407 show promise as vaginal medication preparations for the management of a thin endometrium.