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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

Hydrochlorothiazide, meets USP testing specifications

Sigma-Aldrich

Hydrochlorothiazide, crystalline

Supelco

Acetonitrile, analytical standard

Sigma-Aldrich

Acetonitrile, HPLC Plus, ≥99.9%, poly-coated bottles

Supelco

Hydrochlorothiazide, Pharmaceutical Secondary Standard; Certified Reference Material

Sigma-Aldrich

Acetonitrile, electronic grade, 99.999% trace metals basis

Sigma-Aldrich

Acetonitrile, anhydrous, 99.8%

Sigma-Aldrich

Acetonitrile, ACS reagent, ≥99.5%

Supelco

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

Sigma-Aldrich

Methanol-¹²C, 99.95 atom % ¹²C

Sigma-Aldrich

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

USP

Methyl alcohol, United States Pharmacopeia (USP) Reference Standard

Sigma-Aldrich

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

Sigma-Aldrich

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

Sigma-Aldrich

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

Sigma-Aldrich

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

Sigma-Aldrich

Acetonitrile, HPLC Plus, ≥99.9%

USP

Hydrochlorothiazide, United States Pharmacopeia (USP) Reference Standard

Sigma-Aldrich

Acetonitrile, ≥99.5%, ACS reagent

Sigma-Aldrich

Acetonitrile, suitable for DNA synthesis, ≥99.9% (GC)

Sigma-Aldrich

Acetonitrile, biotech. grade, ≥99.93%

Sigma-Aldrich

Acetonitrile, ReagentPlus^®, 99%

Sigma-Aldrich

Acetonitrile, ≥99.5% (GC)

USP

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

Sigma-Aldrich

Ultrapure Acetonitrile

Sigma-Aldrich

Acetonitrile, AR, ≥99.5%

Cilazapril, European Pharmacopoeia (EP) Reference Standard

Sigma-Aldrich

Acetonitrile, for preparative HPLC, ≥99.8% (GC)

Sigma-Aldrich

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

Sigma-Aldrich

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