Pharmaceutical Composition of Hydrochlorothiazideβ-Cyclo-dextrin Preparation by Three Different Methods, Physico-Chemical Characterization and In Vivo Diuretic Activity Evaluation 英文参考文献.docVIP

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Pharmaceutical Composition of Hydrochlorothiazideβ-Cyclo-dextrin Preparation by Three Different Methods, Physico-Chemical Characterization and In Vivo Diuretic Activity Evaluation 英文参考文献.doc

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Pharmaceutical Composition of Hydrochlorothiazideβ-Cyclo-dextrin Preparation by Three Different Methods, Physico-Chemical Characterization and In Vivo Diuretic Activity Evaluation 英文参考文献

Molecules 2011, 16, 4482-4499; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Pharmaceutical Composition of Hydrochlorothiazide:β-Cyclo- dextrin: Preparation by Three Different Methods, Physico-Chemical Characterization and In Vivo Diuretic Activity Evaluation Maria Arlete Silva Pires 1, Robson Augusto Souza dos Santos 2 and Rubén Dario Sinisterra 1,* 1 Departamento de Química, ICEx, Universidade Federal de Minas Gerais, Avenida Pres. Ant?nio Carlos 6627, 31270-901, Belo Horizonte, Brazil 2 Departamento de Fisiologia e Biofísica, ICB, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Brazil * Author to whom correspondence should be addressed; E-Mail: sinisterra@ufmg.br; Tel.: +55-31-3409-5778; Fax: +55-31-3409-5700. Received: 29 April 2011; in revised form: 19 May 2011 / Accepted: 23 May 2011 / Published: 27 May 2011 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