title: Sulfobutyl ether(7) β-cyclodextrin (SBE(7) β-CD) carbamazepine complex: preparation, characterization, molecular modeling, and evaluation of in vivo anti-epileptic activity.
abstract: The objective of the present investigation was to study the ability of sulfobutyl ether(7)-β-cyclodextrin to form an inclusion complex with carbamazepine, an anti-epileptic drug with poor water solubility. The formation of the complex was carried out using the industrially feasible spray-drying method. The inclusion complex and physical mixtures were characterized by various techniques such as differential scanning calorimetry (DSC), infrared (IR), nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and molecular modeling. The DSC, IR, and NMR studies confirmed the formation of an inclusion complex between carbamazepine and sulfobutyl ether(7) β-cyclodextrin whereas XRD studies indicated an amorphous nature of the inclusion complex. Molecular modeling studies disclosed different modes of interaction between carbamazepine and sulfobutyl ether(7) β-cyclodextrin with good correlation with experimental observations. The inclusion complex exhibited significantly higher in vitro dissolution profile as compared with pure carbamazepine powder. The in vivo anti-epileptic activity of carbamazepine/sulfobutyl ether(7) β-cyclodextrin complex was evaluated in pentylenetetrazole-induced convulsions model. The carbamazepine/sulfobutyl ether(7) β-cyclodextrin complex showed significantly higher anti-epileptic activity (p <0.01) as compared with that of carbamazepine suspension on oral administration.
authors.affiliation: Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz, Mumbai, India.
authors.forename: Ankitkumar S
authors.initials: AS
authors.lastname: Jain
authors.forename: Abhijit A
authors.initials: AA
authors.lastname: Date
authors.forename: Raghuvir R S
authors.initials: RR
authors.lastname: Pissurlenkar
authors.forename: Evans C
authors.initials: EC
authors.lastname: Coutinho
authors.forename: Mangal S
authors.initials: MS
authors.lastname: Nagarsenker
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D002220:Carbamazepine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004827:Epilepsy / Q000139:chemically induced / Q000517:prevention & control*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008958:Models, Molecular; D010433:Pentylenetetrazole; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013678:Technology, Pharmaceutical / Q000379:methods; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000927:Anticonvulsants; D004337:Drug Carriers; C103513:SBE7-beta-cyclodextrin; D047392:beta-Cyclodextrins; D002220:Carbamazepine; D010433:Pentylenetetrazole