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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

Methanol, anhydrous, 99.8%

Supelco

Methanol, analytical standard

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Oxymetazoline hydrochloride, ≥99%, solid

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Acetonitrile solution, contains 0.1 % (v/v) formic acid, suitable for HPLC

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Methanol solution, contains 0.10 % (v/v) formic acid, UHPLC, suitable for mass spectrometry (MS), ≥99.5%

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Methanol, Pharmaceutical Secondary Standard; Certified Reference Material

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Methanol, ACS reagent, ≥99.8%

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Cilazapril impurity D, European Pharmacopoeia (EP) Reference Standard

Oxymetazoline hydrochloride, European Pharmacopoeia (EP) Reference Standard

USP

Oxymetazoline hydrochloride, United States Pharmacopeia (USP) Reference Standard

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Residual Solvent - Acetonitrile, Pharmaceutical Secondary Standard; Certified Reference Material

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Methyl alcohol, United States Pharmacopeia (USP) Reference Standard