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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

Sigma-Aldrich

Oxymetazoline hydrochloride, ≥99%, solid

Sigma-Aldrich

Methanol, NMR reference standard

Sigma-Aldrich

Methanol, HPLC Plus, ≥99.9%

Sigma-Aldrich

Methanol, suitable for HPLC, gradient grade, suitable as ACS-grade LC reagent, ≥99.9%

Sigma-Aldrich

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

Sigma-Aldrich

Methanol, suitable for HPLC, ≥99.9%

Supelco

Methanol, Pharmaceutical Secondary Standard; Certified Reference Material

Sigma-Aldrich

Methanol, ACS reagent, ≥99.8%

Sigma-Aldrich

Methanol, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.8% (GC)

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Methanol, puriss., meets analytical specification of Ph Eur, ≥99.7% (GC)

Sigma-Aldrich

Methanol, BioReagent, ≥99.93%

Cilazapril impurity D, European Pharmacopoeia (EP) Reference Standard

Supelco

Acetonitrile(Neat), Pharmaceutical Secondary Standard; Certified Reference Material

Sigma-Aldrich

Methanol, ACS reagent, ≥99.8%

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Methanol, Absolute - Acetone free

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Methanol, ACS reagent, ≥99.8%

Sigma-Aldrich

Methanol, ACS spectrophotometric grade, ≥99.9%

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Methanol, Laboratory Reagent, ≥99.6%

Oxymetazoline hydrochloride, European Pharmacopoeia (EP) Reference Standard

USP

Oxymetazoline hydrochloride, United States Pharmacopeia (USP) Reference Standard

Supelco

Residual Solvent - Acetonitrile(solution in DMSO), 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.

Sigma-Aldrich

Acetonitrile, electronic grade, 99.999% trace metals basis

Sigma-Aldrich

Hydrochlorothiazide, meets USP testing specifications

Sigma-Aldrich

Hydrochlorothiazide, crystalline

Sigma-Aldrich

Acetonitrile, anhydrous, 99.8%