title: Comparative Solid-State Stability of Perindopril Active Substance vs. Pharmaceutical Formulation.
abstract: This paper presents the results obtained after studying the thermal stability and decomposition kinetics of perindopril erbumine as a pure active pharmaceutical ingredient as well as a solid pharmaceutical formulation containing the same active pharmaceutical ingredient (API). Since no data were found in the literature regarding the spectroscopic description, thermal behavior, or decomposition kinetics of perindopril, our goal was the evaluation of the compatibility of this antihypertensive agent with the excipients in the tablet under ambient conditions and to study the effect of thermal treatment on the stability of perindopril erbumine. ATR-FTIR (Attenuated Total Reflectance Fourier Transform Infrared) spectroscopy, thermal analysis (thermogravimetric mass curve (TG-thermogravimetry), derivative thermogravimetric mass curve (DTG), and heat flow (HF)) and model-free kinetics were chosen as investigational tools. Since thermal behavior is a simplistic approach in evaluating the thermal stability of pharmaceuticals, in-depth kinetic studies were carried out by classical kinetic methods (Kissinger and ASTM E698) and later with the isoconversional methods of Friedman, Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa. It was shown that the main thermal degradation step of perindopril erbumine is characterized by activation energy between 59 and 69 kJ/mol (depending on the method used), while for the tablet, the values were around 170 kJ/mol. The used excipients (anhydrous colloidal silica, microcrystalline cellulose, lactose, and magnesium stearate) should be used in newly-developed generic solid pharmaceutical formulations, since they contribute to an increased thermal stability of perindopril erbumine.
authors.affiliation: Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, 2 Eftimie Murgu, 300041 Timisoara, Romania. buda.valentina.oana@gmail.com.
authors.forename: Valentina
authors.initials: V
authors.lastname: Buda
authors.affiliation: Faculty of Medicine, Victor Babes University of Medicine and Pharmacy, 2 Eftimie Murgu, 300041 Timisoara, Romania. andorminodora@gmail.com.
authors.forename: Minodora
authors.initials: M
authors.lastname: Andor
authors.affiliation: Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, 2 Eftimie Murgu, 300041 Timisoara, Romania. afulias@umft.ro.
authors.forename: Adriana
authors.initials: A
authors.lastname: Ledeti
authors.affiliation: Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, 2 Eftimie Murgu, 300041 Timisoara, Romania. ionut.ledeti@umft.ro.
authors.forename: Ionut
authors.initials: I
authors.lastname: Ledeti
authors.affiliation: Research Centre for Thermal Analysis in Environmental Problems, West University of Timisoara, 300115 Timisoara, Romania. gabriela_vlase@e-uvt.ro.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Vlase
authors.affiliation: Research Centre for Thermal Analysis in Environmental Problems, West University of Timisoara, 300115 Timisoara, Romania. titus_vlase@e-uvt.ro.
authors.forename: Titus
authors.initials: T
authors.lastname: Vlase
authors.affiliation: Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, 2 Eftimie Murgu, 300041 Timisoara, Romania. carmencristescu@umft.ro.
authors.forename: Carmen
authors.initials: C
authors.lastname: Cristescu
authors.affiliation: Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, 2 Eftimie Murgu, 300041 Timisoara, Romania. mavoicu@yahoo.com.
authors.forename: Mirela
authors.initials: M
authors.lastname: Voicu
authors.affiliation: Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, 2 Eftimie Murgu, 300041 Timisoara, Romania. lianads@yahoo.com.
authors.forename: Liana
authors.initials: L
authors.lastname: Suciu
authors.affiliation: Faculty of Medicine, Victor Babes University of Medicine and Pharmacy, 2 Eftimie Murgu, 300041 Timisoara, Romania. tomescu.mirela@umft.ro.
authors.forename: Mirela Cleopatra
authors.initials: MC
authors.lastname: Tomescu
mesh_terms: D004339:Drug Compounding; D004355:Drug Stability; D007700:Kinetics; D020913:Perindopril / Q000737:chemistry / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D013818:Thermogravimetry
chemical_list: D020913:Perindopril
keywords: ASTM E698; comparative stability; decomposition; isoconversional kinetic study; perindopril erbumine; perindopril tert-butylamine; pharmaceutical formulation; thermal stability