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

60004

Sigma-Aldrich

Acetonitrile, ≥99.5% (GC)

Y0001494

Hydrochlorothiazide for peak identification, European Pharmacopoeia (EP) Reference Standard

1424109

USP

Methyl alcohol, United States Pharmacopeia (USP) Reference Standard

C2174000

Cilazapril, European Pharmacopoeia (EP) Reference Standard

H-001

Supelco

Hydrochlorothiazide solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant^®

H1200000

Hydrochlorothiazide, European Pharmacopoeia (EP) Reference Standard

1601340

USP

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

110086

Sigma-Aldrich

Acetonitrile, ReagentPlus^®, 99%

33019

Sigma-Aldrich

Acetonitrile, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥99.5% (GC)

34881

Sigma-Aldrich

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

PHR1032

Supelco

Hydrochlorothiazide, Pharmaceutical Secondary Standard; Certified Reference Material

606723

Sigma-Aldrich

Methanol-¹²C, 99.95 atom % ¹²C

721956

Sigma-Aldrich

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

45983

Supelco

Acetonitrile, analytical standard

50387

Supelco

Acetonitrile, suitable for HPLC, gradient grade, ≥99.9% (GC)

437557

Sigma-Aldrich

Acetonitrile, ≥99.5%, ACS reagent

650188

Sigma-Aldrich

Methanol solution, (Methanol:Dimethyl sulfoxide 1:1 (v/v))

733466

Sigma-Aldrich

Acetonitrile, electronic grade, 99.999% trace metals basis

360457

Sigma-Aldrich

Acetonitrile, ACS reagent, ≥99.5%

675415

Sigma-Aldrich

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

34998

Sigma-Aldrich

Acetonitrile, HPLC Plus, ≥99.9%

271004

Sigma-Aldrich

Acetonitrile, anhydrous, 99.8%

494445

Sigma-Aldrich

Acetonitrile, biotech. grade, ≥99.93%

H2910

Sigma-Aldrich

Hydrochlorothiazide, meets USP testing specifications

632546

Supelco

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

439134

Sigma-Aldrich

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

34442

Sigma-Aldrich

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

34851

Sigma-Aldrich

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

H4759

Sigma-Aldrich

Hydrochlorothiazide, crystalline

1314009

USP

Hydrochlorothiazide, United States Pharmacopeia (USP) Reference Standard