title: Preparation and Evaluation of Diosgenin Nanocrystals to Improve Oral Bioavailability.
abstract: Diosgenin (DSG), a well-known steroid sapogenin derived from Dioscorea nipponica Makino and Dioscorea zingiberensis Wright, has a variety of bioactivities. However, it shows low oral bioavailability due to poor aqueous solubility and strong hydrophobicity. The present study aimed to develop DSG nanocrystals to increase the dissolution and then improve the oral bioavailability and biopharmaceutical properties of DSG. DSG nanocrystals were prepared by the media milling method using a combination of pluronic F127 and sodium dodecyl sulfate as surface stabilizers. The physicochemical properties of the optimal DSG nanocrystals were characterized using their particle size distribution, morphology, differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy data, and solubility and dissolution test results. Pharmacokinetic studies of the DSG coarse suspension and its nanocrystals were performed in rats. The particle size and polydispersity index of DSG nanocrystals were 229.0 ± 3.7 nm and 0.163 ± 0.064, respectively. DSG retained its original crystalline state during the manufacturing process, and its chemical structure was not compromised by the nanonizing process. The dissolution rate of the freeze-dried DSG nanocrystals was significantly improved in comparison with the original DSG. The pharmacokinetic studies showed that the AUC0-72hand Cmaxof DSG nanocrystals increased markedly (p < 0.01) in comparison with the DSG coarse suspension by about 2.55- and 2.01-fold, respectively. The use of optimized nanocrystals is a good and efficient strategy for oral administration of DSG due to the increased dissolution rate and oral bioavailability of DSG nanocrystals.
authors.affiliation: Hebei Province Key Laboratory of Research and Development for Chinese Medicine, Chengde Medical College, Chengde, Hebei, 067000, People's Republic of China. liucuizhexy@163.com.
authors.forename: Cui-Zhe
authors.initials: CZ
authors.lastname: Liu
authors.affiliation: Hebei Province Key Laboratory of Research and Development for Chinese Medicine, Chengde Medical College, Chengde, Hebei, 067000, People's Republic of China.
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Chang
authors.affiliation: Hebei Province Key Laboratory of Research and Development for Chinese Medicine, Chengde Medical College, Chengde, Hebei, 067000, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Hebei Province Key Laboratory of Research and Development for Chinese Medicine, Chengde Medical College, Chengde, Hebei, 067000, People's Republic of China.
authors.forename: He-Fei
authors.initials: HF
authors.lastname: Xue
authors.affiliation: Hebei Province Key Laboratory of Research and Development for Chinese Medicine, Chengde Medical College, Chengde, Hebei, 067000, People's Republic of China.
authors.forename: Xi-Gang
authors.initials: XG
authors.lastname: Liu
authors.affiliation: Hebei Province Key Laboratory of Research and Development for Chinese Medicine, Chengde Medical College, Chengde, Hebei, 067000, People's Republic of China.
authors.forename: Pei
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, People's Republic of China. graham_pharm@aliyun.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D004144:Diosgenin / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005612:Freeze Drying / Q000379:methods; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014961:X-Ray Diffraction
chemical_list: D004144:Diosgenin
keywords: bioavailability; diosgenin; media milling; nanocrystals; pharmacokinetics