Development and In-vitro Evaluation of a Contraceptive Vagino-Adhesive Propranolol Hydrochloride Gel

Abstract

The objective of the present investigation was to develop and evaluate a contraceptive vagino-adhesive propranolol hydrochloride gel. To achieve this, various mucoadhesive polymers including guar gum (1-4% w/w), sodium alginate (4-7% w/w), xanthan gum (2-5% w/w ), HPMC 4000 (3-5% w/w), Na CMC (4-7% w/w), carbomer 934 and carbomer 940 both in the range of 0.5-2.0% w/w, were dispersed in an aqueous-based solution containing the drug (1.6% w/w). The mucoadhesive properties of the gels were assessed on sheep vaginal mucosa (as model mucosa) in pH 4.5 citrate-phosphate buffer at 37°C. Formulations containing charged functional groups in their polymeric structure, showed higher mucoadhesive strengths in comparison to those composed of neutral polymers. In-vitro drug release profiles of the gels were determined in pH 4.5 citrate-phosphate buffer. Results indicated that, only formulation F13 (containing sodium alginate 6.5% w/w), could release its drug over 12 h, with a burst release at the initial phase followed by a sustained release pattern. This formulation, which showed a good mucoadhesive strength (386.97 ± 9.31 mN), was considered as the final formulation and underwent complementary tests including determination of drug content and duration of mucoadhesion. Its drug content was found to be 101.05 ± 0.106% (n = 3) and it attached to the model mucosa for more than 10 h. In conclusion, formulation F13 was considered as the most desirable formulation as it exhibited appropriate mucoadhesive properties while having the potential of providing an immediate contraceptive effect, followed by a prolonged drug release which is assumed to render longer contraceptive efficacy.