title: Pharmaceutical composition of hydrochlorothiazide:β-cyclo-dextrin: preparation by three different methods, physico-chemical characterization and in vivo diuretic activity evaluation.
abstract: Hydrochlorothiazide is a common diuretic antihypertensive drug of the thiazide family. Its poor aqueous solubility is one of the reasons for its limited bioavailability after oral administration. This work aimed at the development of a hydrochlorothiazide:β-cyclodextrin (HTZ:β-CD) pharmaceutical composition in order to improve water solubility and bioavailability of the drug. The HTZ:β-CD complexes were prepared by three different methods: spray-drying, freeze-drying and fluid bed. Complexes were characterized by thermal analysis, Fourier transform-infrared (FTIR) spectroscopy, powder X-ray diffractometry, NMR (2D-ROESY), scanning electron microscopy (SEM), particle analysis and intrinsic dissolution. The findings reveal that three binary systems prepared presented better solubility results in comparison with free HTZ. Increased diuretic effect was observed to HTZ:β-CD obtained by fluid bed in comparison to free drug in rats. Results taken together suggest that pharmacological effect of HTZ in complex was increased by solubility improvement promoted by cyclodextrin.
authors.affiliation: Departamento de Química, ICEx, Universidade Federal de Minas Gerais, Avenida Pres. Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil.
authors.forename: Maria Arlete Silva
authors.initials: MA
authors.lastname: Pires
authors.forename: Robson Augusto
authors.initials: RA
authors.lastname: Souza Dos Santos
authors.forename: Rubén Dario
authors.initials: RD
authors.lastname: Sinisterra
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D004232:Diuretics / Q000737:chemistry* / Q000494:pharmacology*; D006852:Hydrochlorothiazide / Q000737:chemistry* / Q000494:pharmacology*; D007671:Kidney Concentrating Ability / Q000187:drug effects; D008297:Male; D019906:Nuclear Magnetic Resonance, Biomolecular; D011208:Powders / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004232:Diuretics; D011208:Powders; D047392:beta-Cyclodextrins; D006852:Hydrochlorothiazide