title: Cilazapril stability in the presence of hydrochlorothiazide in model mixtures and fixed dose combination.
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.
authors.affiliation: Department of Pharmaceutical Chemistry, Poznań University of Medical Sciences, 6 Grunwaldzka St., 60-780 Poznań, Poland.
authors.forename: Sylwia K
authors.initials: SK
authors.lastname: Paszun
authors.affiliation: Department of Pharmaceutical Chemistry, Poznań University of Medical Sciences, 6 Grunwaldzka St., 60-780 Poznań, Poland.
authors.forename: Beata J
authors.initials: BJ
authors.lastname: Stanisz
authors.affiliation: Department of Pharmaceutical Chemistry, Poznań University of Medical Sciences, 6 Grunwaldzka St., 60-780 Poznań, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gradowska
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D000959:Antihypertensive Agents / Q000737:chemistry*; D002384:Catalysis; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D017315:Cilazapril / Q000737:chemistry*; D004232:Diuretics / Q000737:chemistry*; D004338:Drug Combinations; D004349:Drug Packaging; D004355:Drug Stability; D004356:Drug Storage; D006852:Hydrochlorothiazide / Q000737:chemistry*; D007700:Kinetics; D008956:Models, Chemical; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000737:chemistry
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004232:Diuretics; D004338:Drug Combinations; D013607:Tablets; D014867:Water; D006852:Hydrochlorothiazide; D017315:Cilazapril