title: Use of microcalorimetry in determination of stability of enalapril maleate and enalapril maleate tablet formulations.
abstract: The stability properties of enalapril maleate (EM) and of different tablet formulations including EM were studied by isothermal microcalorimetry and by high performance liquid chromatography (HPLC). It was shown that water content of the sample and elevated temperature have a high impact on stability properties of the substance itself and of the formulations including this substance. The degradation is more extensive at higher water content and at elevated temperature. The type of the tablet formulation (5 or 20mg EM tablet formulation) also has an impact: the 5 EM tablet formulation is the less stable one. The heat output of individual tablet formulations was used to evaluate the enthalpy changes and to calculate the difference in the amount of degraded EM between various samples. These results agreed satisfactorily with those obtained by HPLC. Isothermal microcalorimetry proved to be a fast and predictive method that could be used in preformulation studies to accelerate the pharmaceutical development and shorten the time before launching the product to the market.
authors.affiliation: Krka, d.d., Novo mesto, Smarjeska cesta 6, 8501 Novo mesto, Slovenia. zvone.simoncic@krka.biz
authors.forename: Z
authors.initials: Z
authors.lastname: Simoncic
authors.forename: P
authors.initials: P
authors.lastname: Zupancic
authors.forename: R
authors.initials: R
authors.lastname: Roskar
authors.forename: A
authors.initials: A
authors.lastname: Gartner
authors.forename: K
authors.initials: K
authors.lastname: Kogej
authors.forename: V
authors.initials: V
authors.lastname: Kmetec
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004656:Enalapril / Q000737:chemistry*; D011208:Powders; D013607:Tablets; D013816:Thermodynamics; D014867:Water / Q000032:analysis
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D011208:Powders; D013607:Tablets; D014867:Water; D004656:Enalapril