title: Effect of pharmaceutical excipients on the stability of angiotensin-converting enzyme inhibitors in their solid dosage formulations.
abstract: BACKGROUND
  The compatibility studies of moexipril hydrochloride (MOXL), imidapril hydrochloride (IMD), enalapril maleate, (ENA) and lisinopril (LIS) in solid state with magnesium stearate and glyceryl behenate were performed.
  
  
  OBJECTIVE
  The aim of this study was to detect any possible drug-excipient interactions in order to optimize technological process conditions by the selection of the most adequate lubricant.
  
  
  METHODS
  Reversed-phase high-performance liquid chromatography was employed for studying drug-excipient binary mixtures in 1:1 ratio and pure drugs under forced ageing test conditions: temperature 318K (45 °C) and relative humidity range of 50.9%-75.4%. The method had been revalidated prior to use. The degradation rate constants for the binary mixtures and pure substances were calculated.
  
  
  RESULTS
  The experimental results evidenced that moexipril and enalapril degradation accorded with autocatalytic-second-order kinetics, imidapril degradation followed first-order reaction mechanism, and LIS followed reversible first-order reaction mechanism. A degradation pathway for each substance was proposed to account for the observed decomposition products. It was determined that moexipril stability decreased threefold in the presence of magnesium stearate indicating an incompatibility--(4.15 ± 0.12) 10(-3) compared to (1.43 ± 0.32) 10(-6) for moexipril in pure. No interaction between magnesium stearate and the remaining studied compounds was observed. The stability studies of MOXL-glyceryl behenate binary mixture revealed no interaction.
  
  
  CONCLUSIONS
  Magnesium stearate and increased relative humidity induce MOXL instability, while glyceryl behenate is an optimal lubricant, and therefore, it is recommended for moexipril-containing solid formulations. However, for the formulations containing moexipril and magnesium stearate, it is suggested to minimize the humidity level during storage.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Medical Sciences, Poznan, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Stanisz
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Regulska
authors.forename: Jagoda
authors.initials: J
authors.lastname: Kania
authors.forename: Piotr
authors.initials: P
authors.lastname: Garbacki
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004304:Dosage Forms; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005227:Fatty Acids / Q000737:chemistry*; D006358:Hot Temperature; D006813:Humidity; D013229:Stearic Acids / Q000737:chemistry*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004304:Dosage Forms; D005079:Excipients; D005227:Fatty Acids; D013229:Stearic Acids; C086409:glyceryl behenate; C031183:stearic acid