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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

Supelco

Acetonitrile, Pharmaceutical Secondary Standard; Certified Reference Material

Sigma-Aldrich

Methanol-¹²C, 99.95 atom % ¹²C

Supelco

Hydrochlorothiazide, Pharmaceutical Secondary Standard; Certified Reference Material

Sigma-Aldrich

Methanol solution, NMR reference standard, 4% in methanol-d₄ (99.8 atom % D), NMR tube size 3 mm × 8 in.

Cilazapril, European Pharmacopoeia (EP) Reference Standard

Supelco

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

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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, ≥99.5%, ACS reagent

USP

Methyl alcohol, United States Pharmacopeia (USP) Reference Standard

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Acetonitrile, ≥99.5% (GC)

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Acetonitrile, ReagentPlus^®, 99%

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Ultrapure Acetonitrile

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USP

Residual Solvent Class 2 - Acetonitrile, United States Pharmacopeia (USP) Reference Standard

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Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%

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Acetonitrile, suitable for HPLC-GC, ≥99.8% (GC)

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Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%

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Acetonitrile, for HPLC, for UV, ≥99.9% (GC)

Supelco

Acetonitrile, analytical standard

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Hydrochlorothiazide, crystalline

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Acetonitrile, biotech. grade, ≥99.93%

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Acetonitrile, HPLC Plus, ≥99.9%

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Acetonitrile, ACS reagent, ≥99.5%

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Acetonitrile solution, contains 10.0% acetone, 0.05% formic acid, 40.0% 2-propanol

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