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

[ Vol. 18 , Issue. 5 ]

Author(s):

Xi Liang, Yabing Hua, Qian Liu, Zhiguo Li, Fanglin Yu, Jing Gao, Hui Zhang* and Aiping Zheng*   Pages 620 - 633 ( 14 )

Abstract:


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.

Keywords:

Testosterone undecanoate, solid SEDDS, ternary phase diagram, neusilin US2, dissolution, pharmacokinetics.

Affiliation:

TEAM Academy of Pharmaceutical Sciences Co. Ltd., Beijing 102488, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850

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