Preparation and In Vitro and In Vivo Evaluation of Rectal In Situ Gel of Meloxicam Hydroxypropyl-β-cyclodextrin Inclusion Complex
Xiaomeng Lei,
Guansheng Zhang,
Tao Yang,
Yuhuan Wu,
Ying Peng,
Tiantian Wang,
Dongxun Li,
Qian Liu,
Canjian Wang,
Guosong Zhang
Affiliations
Xiaomeng Lei
National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China
Guansheng Zhang
National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China
Tao Yang
College of Chinese Medicine and Life Science, Jiangxi University of Chinese Medicine, Nanchang 330004, China
Yuhuan Wu
National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China
Ying Peng
National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China
Tiantian Wang
National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China
Dongxun Li
National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China
Qian Liu
National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China
Canjian Wang
National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China
Guosong Zhang
National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Jiangxi University of Chinese Medicine, Nanchang 330006, China
Meloxicam (MLX) is one of the most effective NSAIDs, but its poor water solubility and low bioavailability limit its clinical application. In this study, we designed a thermosensitive in situ gel of the hydroxypropyl-β-cyclodextrin inclusion complex (MLX/HP-β-CD-ISG) for rectal delivery to improve bioavailability. The best method for preparing MLX/HP-β-CD was the saturated aqueous solution method. The optimal inclusion prescription was optimized using an orthogonal test, and the inclusion complex was evaluated via PXRD, SEM, FTIR and DSC. Then, MLX/HP-β-CD-ISG was characterized regarding the gel properties, release in vitro, and pharmacokinetics in vivo. The inclusion rate of the inclusion complex obtained via the optimal preparation process was 90.32 ± 3.81%. The above four detection methods show that MLX is completely embedded in the HP-β-CD cavity. The developed MLX/HP-β-CD-ISG formulation has a suitable gelation temperature of 33.40 ± 0.17 °C, a gelation time of 57.33 ± 5.13 s, pH of 7.12 ± 0.05, good gelling ability and meets the requirements of rectal preparations. More importantly, MLX/HP-β-CD-ISG significantly improved the absorption and bioavailability of MLX in rats, prolonging the rectal residence time without causing rectal irritation. This study suggests that the MLX/HP-β-CD-ISG can have a wide application prospect with superior therapeutic benefits.
