Preparation and In Vitro and In Vivo Evaluation of a Testosterone Film Forming Gel for the Treatment of Hypoactive Sexual Desire Disorder in Women.

ABSTRACT

Hypoactive sexual desire disorder (HSDD) is one of the most common sexual complaints in women. Currently, there is an unmet need for a drug treatment for this disorder. The purpose of this study was to develop a testosterone (TS) film forming gel used for women to treat HSDD by measuring the tackiness, peel adhesion force, tensile strength, and elasticity of the formulation. Diethylene glycol monoethyl ether (Transcutol P), an efficient penetration enhancer, was added to the optimized formulation and the transdermal permeation characteristics in vitro were studied using Franz-diffusion cells. The quantitative determination of TS was performed by high-performance liquid chromatography (HPLC). After 24 h, Transcutol P at 3% had the largest cumulative amount of drug and enhancement ratio of TS of 75.14 µg/cm2 and 2.82, respectively. After the screening of film forming polymers and penetration enhancers, the optimal formulation was as follows glycerol (1%, w/w); 12.5% sodium carboxymethylcellulose (CMC-Na) aqueous solution (0.5%, w/w); 2.5% Carbomer ethanol solution (0.5%, w/w); Transcutol P ethanol solution (3%, w/w) containing 0.5% TS; and 8% Poly vinyl alcohol (PVA) aqueous solution (30%, w/w). The optimized film forming gel had good uniformity and the release of TS in vitro was close to 100% within 24 h. In vivo studies showed the formulations had optimal area under blood drug concentration curve values in the order of 3% Transcutol P > 1% Transcutol P > 5% Transcutol P > control preparation. The formulation with 3% Transcutol P provided the highest permeation effect both in vitro and in vivo. The safety of this formulation was further evaluated with a skin irritation test. It could effectively improve the rabbit skin irritation observed with a marketed transdermal patch Androderm®. The present study provides a promising approach for the development of a novel TS film forming gel for the treatment of HSDD in women.