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  • Cilazapril stability in the presence of hydrochlorothiazide in model mixtures and fixed dose combination.

Cilazapril stability in the presence of hydrochlorothiazide in model mixtures and fixed dose combination.

Acta poloniae pharmaceutica (2014-01-05)
Sylwia K Paszun, Beata J Stanisz, Agnieszka Gradowska
ABSTRACT

The presented study aimed at the evaluation of hydrochlorothiazide influence on cilazapril stability in model mixture and fixed dose tablet formulation. The degradation of cilazapril in the presence of hydrochlorothiazide took place according to autocatalytic reaction kinetic mechanism, described mathematically by Prout-Tompkins equation. Hydrochlorothiazide coexistence with cilazapril in model mixture and fixed dose tablet without blister package accelerated cilazapril degradation in comparison with degradation of cilazapril substance. Values of reaction induction time shortened, while those of observed reaction rate constant increased. Increasing values of relative humidity and temperature have negative impact on cilazapril stability. Determined semi-logarithmic relationships: In k = f(RH) and Arrhenius ln k = f(1/T) are linear and are cilazapril stability predictive. The blister (OPA/Alu/PVC//Alu) package of fixed dose tablets, constitutes absolute moisture protection and prevent cilazapril--hydrochlorothiazide interaction occurrence.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%
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Acetonitrile, anhydrous, 99.8%
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Acetonitrile, electronic grade, 99.999% trace metals basis
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Hydrochlorothiazide, meets USP testing specifications
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Acetonitrile, biotech. grade, ≥99.93%
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Hydrochlorothiazide, European Pharmacopoeia (EP) Reference Standard
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Acetonitrile, for preparative HPLC, ≥99.8% (GC)
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Hydrochlorothiazide, crystalline
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Residual Solvent Class 2 - Acetonitrile, United States Pharmacopeia (USP) Reference Standard
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Acetonitrile, suitable for HPLC-GC, ≥99.8% (GC)
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Hydrochlorothiazide, Pharmaceutical Secondary Standard; Certified Reference Material
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Oxymetazoline hydrochloride, United States Pharmacopeia (USP) Reference Standard
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