title: Effectiveness of mechanochemical treatment with cyclodextrins on increasing solubility of glimepiride.
abstract: We investigated the enhancement of the solubility of glimepiride (GLM), a poorly water soluble anti-diabetes drug, by cogrinding it with various cyclodextrins (CDs) using a ball mill. The phase solubility profiles of GLM with beta-CD and its derivatives were classified as A(L)-type, indicating the formation of a 1 : 1 stoichiometric water-soluble complex. When GLM crystals were coground with beta-CD using a ball mill for 48 h, the aqueous solubility of GLM increased to approximately 250 microg/mL. The powder X-ray diffraction pattern showed that the peak intensity of crystalline GLM decreased after cogrinding. Endothermic peaks of around 208 degrees C, which were assigned to the fusion of GLM crystals, disappeared in the DSC measurement of the ground mixture. After cogrinding, two sharp peaks assigned to sulfonylurea and benzoyl carbonyl stretching bands varied to broaden the peak to around 1700 cm(-1) in the C=O stretching region. These results suggested the formation of a complex between GLM and beta-CD during cogrinding.
authors.affiliation: Sanofi-Aventis K.K, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Iwata
authors.forename: T
authors.initials: T
authors.lastname: Fukami
authors.forename: D
authors.initials: D
authors.lastname: Kawashima
authors.forename: M
authors.initials: M
authors.lastname: Sakai
authors.forename: T
authors.initials: T
authors.lastname: Furuishi
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Tomono
authors.forename: H
authors.initials: H
authors.lastname: Ueda
mesh_terms: D002152:Calorimetry, Differential Scanning; D003505:Cyclodextrins / Q000737:chemistry*; D004339:Drug Compounding; D005079:Excipients; D007004:Hypoglycemic Agents / Q000737:chemistry*; D007202:Indicators and Reagents; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013453:Sulfonylurea Compounds / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D003505:Cyclodextrins; D005079:Excipients; D007004:Hypoglycemic Agents; D007202:Indicators and Reagents; D013453:Sulfonylurea Compounds; C057619:glimepiride