Evaluation of testosterone compatibility with different excipients for the development of a self-emulsifying drug delivery system

Testosterone is a cholesterol-derived steroidal hormone responsible for male sexual characteristics. Besides undergoing intense hepatic and intestinal metabolism, it presents low aqueous solubility and low intestinal permeability. Various strategies have been investigated to improve the bioavailability of poorly water-soluble such as testosterone, including the use of lipid systems. The main goal of this work was to carry out a pre-formulation study for the development a liquid self-emulsifying drug delivery system (L-SEDDS) with testosterone. The compatibility of the drug with oils and surfactants was investigated using DSC, TG, FTIR and isothermal stress test (IST). Interactions with testosterone were identified for oleic acid, Span 80 and Castor oil, in which greater changes were observed in the DSC and DTG thermal profiles. The incompatibility of the testosterone with these excipients was confirmed by the IST after 15 or 30 days of storage at 50 degrees C. A phase diagram was constructed using different proportions (w/w) of Captex 355, Tween 80 and Span 85. Formulations were characterized for size, PdI and zeta potential. F4 showed the highest zeta potential values (- 30.70 +/- 2.28 mV and - 33.25 +/- 1.77 mV) and lowest PdI values (0.232 +/- 0.001 and 0.244 +/- 0.011) (before and after drug incorporation, respectively). The pre-formulation studies enabled a rational selection of excipients for the development of L-SEDDS containing testosterone, thus reinforcing the importance and applicability of analytical and thermo-analytical techniques in the development of new formulations.