Physicochemical evaluation of PVP-thiazide diuretic interactions in co-spray-dried composites--analysis of glass transition composition relationships.

The aim of this study was to evaluate the possible interactions in the solid state between the thiazide diuretics: bendroflumethiazide (BFMT), hydroflumethiazide (HFMT) and hydrochlorothiazide (HCT) and polyvinylpyrrolidone (PVP) following processing. The glass transition temperatures (T(g)s) of a range of binary co-spray-dried PVP-thiazide composites were determined and compared to the predictions of the Gordon-Taylor, Fox, Couchman-Karasz, Kwei and Schneider equations. The solid composites of the thiazide diuretics and PVP were prepared by a spray drying technique. Properties of composites were determined with the use of helium pycnometry and FTIR spectroscopy. For many systems studied the experimentally detected T(g)s exhibited large positive deviations when compared with the values predicted by the Gordon-Taylor, Fox and Couchman-Karasz equations. The data was better fitted by the Schneider equation consistent with a drug-polymer interaction. FTIR analysis revealed that strong hydrogen bonding between the sulphonamide groups of the thiazide diuretics and the PVP molecule was responsible for the increase in the T(g)s. Additionally, in the case of BFMT-PVP composites, an interaction between the phenyl group and polymer ring was apparent. Glass transition-composition behaviour for amorphous drug-PVP composites deviated from the predictions of the commonly used Gordon-Taylor equation. Deviations were consistent with interactions between the components in the amorphous mixtures. The Schneider equation may be successfully applied to fit the Tg-composition profiles obtained, where other models fail to give good predictions.