Cucurbita pepo L. subsp. pepo (green zucchini variety) contains abundant bioactive compounds, positioning it as a potential remedy for vaginal dryness based on principles from Persian medicine. This research sought to develop a vaginal cream incorporating green zucchini extract and to investigate its potential for causing vaginal irritation through an in vivo study. A vaginal cream was prepared with 5% aqueous extract from green zucchini. Evaluations included physicochemical characteristics such as visual appearance, pH level, viscosity, ease of spreading, and gallic acid concentration, alongside microbial contamination checks. The formulation underwent stress testing and a six-month accelerated stability assessment; additionally, its irritancy was tested in rabbits over five days. The optimized cream consisted of green zucchini extract (5%), cetyl palmitate (4.2%), octyl dodecanol (11.7%), polysorbate 60 (7.2%), sorbitan monostearate (2.0%), cetostearyl alcohol (12.5%), benzyl alcohol (0.5%), lactic acid (0.1%), and purified water (56.8%). It exhibited appropriate physicochemical and microbiological qualities, including a pH of 4.0 and viscosity of 39.57 Pa.s. Analysis revealed 23 mg gallic acid per 100 g of cream. The product remained stable under stress conditions and during the six-month accelerated stability evaluation. Irritation testing in rabbits showed no evidence of erythema or edema, confirming its tolerability. The vaginal cream derived from green zucchini demonstrated favorable physicochemical properties and a non-irritating profile, indicating its viability as a safe, standardized option; nevertheless, additional human clinical trials are required.
