Pharmaceutical composition of hydrochlorothiazide:β-cyclo-dextrin: preparation by three different methods, physico-chemical characterization and in vivo diuretic activity evaluation

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Maria Arlete Silva PiresRubén Dario Sinisterra

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.

Citations

Feb 26, 2013·International Journal of Molecular Sciences·Naoko IkutaSeiichi Matsugo
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May 8, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chi-Ya HuangHui-Ting Chang
Oct 3, 2017·Drug Delivery and Translational Research·Nicolaos ScoutarisDennis Douroumis
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Jan 21, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hui-Ting ChangShang-Tzen Chang

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Methods Mentioned

BETA
X-ray
NMR
scanning electron microscopy

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