The use of microcalorimetry and HPLC for the determination of degradation kinetics and thermodynamic parameters of Perindopril Erbumine in aqueous solutions

Perindopril Erbumine (PER) is one of the newly used angiotensin-converting enzyme inhibitors (ACE inhibitors) and is used for the treatment of patients with hypertension and symptomatic heart failure. It has two main degradation pathways, i.e. the degradation by hydrolysis and the degradation by cyc...

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Bibliographic Details
Published in:International journal of pharmaceutics 2008-05, Vol.356 (1), p.200-205
Main Authors: Simončič, Z., Roškar, R., Gartner, A., Kogej, K., Kmetec, V.
Format: Article
Language:English
Subjects:
Angiotensin-Converting Enzyme Inhibitors - chemistry
Biological and medical sciences
Calorimetry - methods
Chemistry, Pharmaceutical
Chromatography
Chromatography, High Pressure Liquid - methods
Degradation kinetic
Drug Stability
Drug Storage
General pharmacology
Hydrogen-Ion Concentration
Isothermal microcalorimetry
Kinetics
Medical sciences
Perindopril
Perindopril - chemistry
Pharmaceutical Solutions
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Solution stability
Thermodynamics
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Summary:Perindopril Erbumine (PER) is one of the newly used angiotensin-converting enzyme inhibitors (ACE inhibitors) and is used for the treatment of patients with hypertension and symptomatic heart failure. It has two main degradation pathways, i.e. the degradation by hydrolysis and the degradation by cyclization. An isothermal heat conduction microcalorimetry (MC) and high pressure liquid chromatography (HPLC) were used for the characterization of aqueous solutions of PER and its stability properties. The rates of heat evolved during degradation of perindopril were measured by MC as a function of temperature and pH and from these data rate constant and change in enthalpy of the reactions were determined. With the HPLC method the concentration of perindopril and its degradation products were measured as a function of time in aqueous solutions of different pH that were stored at different temperatures. We demonstrated that reactions of degradation of perindopril at observed conditions follow the first order kinetics. The Arrhenius equation for each pH was determined. At pH 6.8 only one degradation pathway is present, i.e. the degradation by hydrolysis. Degradation constants for this pathway calculated from MC data are in good agreement with those obtained from HPLC. MC as a non-specific technique was shown to be useful in studies of PER when one reaction was present in the sample and also when more chemical and physical processes were simultaneously running.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2008.01.031