Solid Self-Emulsifying Drug Delivery System (Solid SEDDS) for Testosterone Undecanoate: In Vitro and In Vivo Evaluation.

OBJECTIVE: The current study aimed to investigate the potential of Solid Self-Emulsifying Drug Delivery Systems (solid SEDDS) loaded with Testosterone Undecanoate (TU) (solid TUSEDDS). The solid TU-SEDDS was composed of TU, Medium-Chain Triglycerides (MCT, oil), 2- Chloro-1-(chloromethyl) ethyl carbamate (EL-35, surfactant) and polyethylene glycol (PEG400, cosurfactant). It was expected to improve the dissolution and oral bioavailability of TU, as a result of investigating the feasibility of the clinical application of SEDDS. METHODS: First, a TU-SEDDS was developed by using rational blends of components with the good solubilizing ability for TU. Next, a ternary phase diagram was constructed to determine the self-emulsifying region, and the formulation was optimized. Then, the solid TU-SEDDS formulation was established by screening suitable solid adsorptions. Finally, the prepared SEDDS, TUSEDDS and solid TU-SEDDS formulations were evaluated in vitro and in vivo. RESULTS: The size of the solid TU-SEDDS was 189.1 ± 0.23 nm. The Transmission Electron Microscopy (TEM) results showed that the oil droplets were homogenous and spherical with good integrity. The Differential Scanning Calorimetry (DSC) and X-Ray Powder Dffraction (XRD) results indicated that the solid TU-SEDDS formulation almost preserves the amorphous state. Scanning Electron Microscopy (SEM) indicated that neusilin US2 successfully adsorbed the TU-SEDDS. Drug release indicated that the dissolution of the solid TU-SEDDS was faster than that of Andriol Testocaps ®. Furthermore, in vivo pharmacokinetic (PK) studies in Sprague-Dawley (SD) rats showed that the Area Under the Curve (AUC) of the solid TU-SEDDS (487.54±208.80 µg/L×h) was higher than that of Andriol Testocaps® (418.93±273.52 µg/L×h, P < 0.05). In beagles not fed a high-fat diet, the AUC of the solid TU-SEDDS (5.81±4.03 µg/L×h) was higher than that of Andriol Testocaps ® (5.53±3.43 µg/L×h, P > 0.05). In beagles fed a high-fat diet, the AUC of the solid TUSEDDS (38.18±21.90 µg/L×h) was higher than that of Andriol Testocaps® (37.17±13.79 µg/L×h, P > 0.05). CONCLUSION: According to the results of this research, oral solid TU-SEDDS is expected to be another alternative delivery system for the late-onset hypogonadism. This is beneficial to the transformation of existing drug delivery systems into preclinical and clinical studies.