title: Preparation, characterization and in vivo evaluation of a formulation of dantrolene sodium with hydroxypropyl-β-cyclodextrin.
abstract: Dantrolene sodium (Da) is an effective skeletal muscle relaxant. However, its pharmacological effects are severely limited owing to its poor solubility and low oral bioavailability. In order to solve these problems, an inclusion complex using hydroxypropyl-β-cyclodextrin (HP-β-CD) to improve the oral bioavailability of Da was prepared successfully by freeze-drying. The prepared complex was characterized by Powder X-ray diffractometry (PXRD), Fourier transform infrared spectroscopy (FTIR) and evaluated by a dissolution test and a pharmacokinetic study. The results of PXRD and FTIR proved the formation of a complex between Da and HP-β-CD. The dissolution rate of Da was markedly improved from inclusion complex with more than 90% being released within 5min. The in vivo pharmacokinetics of Da and dantrolene sodium-hydroxypropyl-β-cyclodextrin (Da-HP-β-CD) inclusion complex were investigated in rats using a UPLC/MS/MS method. The Cmaxand AUC0-tof the Da-HP-β-CD inclusion complex were 5- and 3-fold higher than that of the Da. These results suggested that the Da-HP-β-CD inclusion complex markedly improved the dissolution rate and bioavailability of Da.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Chen
authors.affiliation: Lizhu Group Lizhu Medicinal Research Institute, Guihua North Road 132, Zhuhai, Guangdong Province, China.
authors.forename: Qijuan
authors.initials: Q
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Lizhu Group Lizhu Medicinal Research Institute, Guihua North Road 132, Zhuhai, Guangdong Province, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, China. Electronic address: lab433@163.com.
authors.forename: Chunjie
authors.initials: C
authors.lastname: Zhao
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000284:Administration, Oral; D000818:Animals; D003620:Dantrolene / Q000008:administration & dosage / Q000097:blood* / Q000138:chemical synthesis*; D004338:Drug Combinations; D004339:Drug Compounding; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014961:X-Ray Diffraction / Q000379:methods; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000097:blood* / Q000138:chemical synthesis*
chemical_list: D004338:Drug Combinations; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D003620:Dantrolene
keywords: Dantrolene sodium; Hydroxypropyl-β-cyclodextrin; Pharmacokinetics; Physicochemical characterization; UPLC/MS/MS