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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

Cilazapril impurity D, European Pharmacopoeia (EP) Reference Standard
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Methanol, NMR reference standard
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Residual Solvent - Acetonitrile(solution in DMSO), Pharmaceutical Secondary Standard; Certified Reference Material
USP
Oxymetazoline hydrochloride, United States Pharmacopeia (USP) Reference Standard
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Methanol, anhydrous, 99.8%
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Oxymetazoline hydrochloride, ≥99%, solid
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Methanol, Laboratory Reagent, ≥99.6%
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Methanol, suitable for HPLC, ≥99.9%
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Methanol, HPLC Plus, ≥99.9%
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Methanol, Absolute - Acetone free
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Methanol, Pharmaceutical Secondary Standard; Certified Reference Material
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Methanol, ACS spectrophotometric grade, ≥99.9%
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Methanol, analytical standard
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Acetonitrile(Neat), Pharmaceutical Secondary Standard; Certified Reference Material
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Methanol, BioReagent, ≥99.93%
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Methanol, ACS reagent, ≥99.8%
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Methanol, ACS reagent, ≥99.8%
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Methanol, puriss., meets analytical specification of Ph Eur, ≥99.7% (GC)
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Methanol, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.8% (GC)
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Methanol, ACS reagent, ≥99.8%
Oxymetazoline hydrochloride, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Methanol, suitable for HPLC, gradient grade, ≥99.9%
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Methanol, suitable for HPLC, gradient grade, suitable as ACS-grade LC reagent, ≥99.9%
Hydrochlorothiazide for peak identification, European Pharmacopoeia (EP) Reference Standard
Cilazapril, European Pharmacopoeia (EP) Reference Standard
Hydrochlorothiazide, European Pharmacopoeia (EP) Reference Standard
USP
Methyl alcohol, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Acetonitrile, for preparative HPLC, ≥99.8% (GC)
Sigma-Aldrich
Acetonitrile, ≥99.9% (GC)
Sigma-Aldrich
Hydrochlorothiazide, crystalline