Purpose The thermal analysis during the physicochemical characterization is a crucial step in pharmaceutical development. A review of the applications of the thermal analysis technique in pharmaceutical research was included in our study. The purpose of this study was the investigation of the thermal behavior of linezolid via the thermogravimetric and derivative thermogravimetric analysis (TGA/DTG) and differential thermal analysis (DTA) measurements. Also, the isothermal analysis of linezolid was studied by a new computational method without the need for practical experiments. Methods The effect of several default programmed heating rates (5, 7.5, 10, and 12.5 °C min−1) was studied. Flynn–Wall–Ozawa (F-W-O), Coats-Redfern (CR), and Arrhenius techniques were utilized to determine the kinetic parameters from TG/DTG curves. Results Linezolid powder performed a polymorphism phenomenon of a liquid–solid transition due to a heat-mediated change from a low-melting metastable form to a higher-melting stable form. The kinetic studies showed a thermal behavior characteristic of (0.3) order at the sharp first TG thermal decomposition phase according to F-W-O and Arrhenius techniques with activation energy (Ea) of 116.49 ± 1.22 kJ mol−1 and frequency factor (A) of 1.80 × 1010 ± 1.18 × 109 min−1. While entropy (∆S), enthalpy (∆H), and free energy (∆G*) of activation were found to be -54.00 ± 0.54 (J mol−1 K−1), 111.74 ± 1.22 (KJ mol−1), and 142.55 ± 1.17 (KJ mol−1), respectively. The new computational isothermal study showed that, when temperature decreased, reaction rates slowed down and thermal degradation took more time overall. The examined reduced-time plot recorded the effect of temperature on thermal degradation reduced time. Conclusion The thermal analysis is a crucial step in the physicochemical characterization. Linezolid has two polymorphic forms. The new computational isothermal analysis is carried out without the need for additional tests at fixed temperatures, which saves time and effort. The examined reduced-time plot provided information on whether or not the process in the temperature range examined is isokinetic in character.

Thermal Analysis and Novel Computational Isothermal Studies on the Antibiotic Linezolid

期刊论文
发表日期：

2025年6月20日

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Hanan I. EL-Shorbagy,
Mona A. Mohamed,
Abd El-Motaleb M. Ramadan,
Alaa El-Gindy,
Ghada M. Hadad,
Fathalla Belal

摘要

Purpose

The thermal analysis during the physicochemical characterization is a crucial step in pharmaceutical development. A review of the applications of the thermal analysis technique in pharmaceutical research was included in our study. The purpose of this study was the investigation of the thermal behavior of linezolid via the thermogravimetric and derivative thermogravimetric analysis (TGA/DTG) and differential thermal analysis (DTA) measurements. Also, the isothermal analysis of linezolid was studied by a new computational method without the need for practical experiments.

Methods

The effect of several default programmed heating rates (5, 7.5, 10, and 12.5 °C min⁻¹) was studied. Flynn–Wall–Ozawa (F-W-O), Coats-Redfern (CR), and Arrhenius techniques were utilized to determine the kinetic parameters from TG/DTG curves.

Results

Linezolid powder performed a polymorphism phenomenon of a liquid–solid transition due to a heat-mediated change from a low-melting metastable form to a higher-melting stable form. The kinetic studies showed a thermal behavior characteristic of (0.3) order at the sharp first TG thermal decomposition phase according to F-W-O and Arrhenius techniques with activation energy (Ea) of 116.49 ± 1.22 kJ mol⁻¹ and frequency factor (A) of 1.80 × 10¹⁰ ± 1.18 × 10⁹ min⁻¹. While entropy (∆S*), enthalpy (∆H*), and free energy (∆G*) of activation were found to be -54.00 ± 0.54 (J mol⁻¹ K⁻¹), 111.74 ± 1.22 (KJ mol⁻¹), and 142.55 ± 1.17 (KJ mol⁻¹), respectively. The new computational isothermal study showed that, when temperature decreased, reaction rates slowed down and thermal degradation took more time overall. The examined reduced-time plot recorded the effect of temperature on thermal degradation reduced time.

Conclusion

The thermal analysis is a crucial step in the physicochemical characterization. Linezolid has two polymorphic forms. The new computational isothermal analysis is carried out without the need for additional tests at fixed temperatures, which saves time and effort. The examined reduced-time plot provided information on whether or not the process in the temperature range examined is isokinetic in character.