title: Solid self-microemulsifying dispersible tablets of celastrol: formulation development, charaterization and bioavailability evaluation.
abstract: The aims of this study were to choose a suitable adsorbent of self-microemulsion and to develop a fine solid self-microemulsifying dispersible tablets for promoting the dissolution and oral bioavailability of celastrol. Solubility test, self-emulsifying grading test, droplet size analysis and ternary phase diagrams test were performed to screen and optimize the composition of liquid celastrol self-microemulsifying drug delivery system (SMEDDS). Then microcrystalline cellulose KG 802 was added as a suitable adsorbent into the optimized liquid celastrol-SMEDDS formulation to prepare the dispersible tablets by wet granulation compression method. The optimized formulation of celastrol-SMEDDS dispersible tablets was finally determinated by the feasibility of the preparing process and redispersibility. The in vitro study showed that the dispersible tablets could disperse in the dispersion medium within 3 min with the average particle size of 25.32 ± 3.26 nm. In vivo pharmacokinetic experiments of rats, the relative bioavailability of celastrol SMEDDS and SMEDDS dispersible tablets compared to the 0.4% CMC-Na suspension was 569 ± 7.07% and 558 ± 6.77%, respectively, while there were no significant difference between the SMEDDS and SMEDDS dispersible tablets. The results suggest the potential use of SMEDDS dispersible tablets for the oral delivery of poorly water-soluble terpenes drugs, such as celastrol.
authors.affiliation: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Xiaole
authors.initials: X
authors.lastname: Qi
authors.affiliation: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Qin
authors.affiliation: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.affiliation: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Chou
authors.affiliation: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China; Yangtze River Pharmaceutical Group, State Key Laboratory for Advanced Formulation Technologies, Taizhou, PR China. Electronic address: zhenghongwu66@cpu.edu.cn.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000818:Animals; D001682:Biological Availability; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D004655:Emulsions; D008055:Lipids / Q000737:chemistry; D008297:Male; D053978:Pentacyclic Triterpenes; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013607:Tablets; D014315:Triterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D004655:Emulsions; D008055:Lipids; D053978:Pentacyclic Triterpenes; D013501:Surface-Active Agents; D013607:Tablets; D014315:Triterpenes; D002482:Cellulose; C050414:celastrol; C109691:microcrystalline cellulose
keywords: Celastrol; Dispersible tablets; Oral bioavailability; Solid self-microemulsifying system (S-SMEDDS)