Open AccessCompatibility by a Nonisothermal Kinetic Study of Azathioprine Associated with Usual Excipients in the Product Quality Review Process
Author(s) -
Carolina R. G. Silva,
Sílvia Ligório Fialho,
Jamile Barbosa,
Bárbara C. R. Araújo,
Guilherme Carneiro,
Rita C. O. Sebastião,
Wagner da Nova Mussel,
María Irene Yoshida,
Maria Betânia de Freitas-Marques
Publication year - 2021
Publication title -
journal of the brazilian chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.337
H-Index - 70
eISSN - 1678-4790
pISSN - 0103-5053
DOI - 10.21577/0103-5053.20200218
Subject(s) - magnesium stearate , thermogravimetry , differential scanning calorimetry , chemical engineering , fourier transform infrared spectroscopy , thermal analysis , materials science , chemistry , nuclear chemistry , dosage form , chromatography , thermal , inorganic chemistry , thermodynamics , physics , engineering
Azathioprine is an immunosuppressive drug for several inflammatory disorders. Due to its clinical relevance, to explore the solid-state properties for excipient compatibility in the product quality review process is essential. Fourier transform infrared spectroscopy, powder X-ray diffraction and thermal analysis (thermogravimetry/derivative thermogravimetry (TG/DTG), differential thermal analysis (DTA), and differential scanning calorimetry (DSC)) were applied. The compatibility studies evidenced that starch pregelatinized, colloidal silicon dioxide, and talc are fully compatible with azathioprine. However, stearic acid, magnesium stearate, and mannitol are incompatible after heat supply at temperatures easily reached by industrial processing. The nonlinear Vyazovkin isoconversional treatment performed the kinetic study of the thermal degradation. The activation energies were determined to clarify the influence of each excipient on the thermal drug stability, an essential procedure in the pharmaceutical development, and all over the commercial live span, in Good Manufacturing Practices.