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Stability evaluation and kinetic study for the atypical antidepressant opipramol

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Abstract

Opipramol is an active pharmaceutical ingredient used as an antidepressant and anxiolytic, being formulated as a dihydrochloride salt, usually in tablets and drops. The aim of the present study was represented by the thermal stability and kinetic evaluation of opipramol dihydrochloride (OPI 2HCl) performed in an oxidative atmosphere on the 30–450 °C temperature range using multiple heating rates (β = 2.5, 5, 7, 10 and 12 °C min−1). Thermogravimetric and derivative thermogravimetric analysis proved the stability of OPI 2HCl up until 150 °C followed by a single mass loss of approximately 80% up until 350 °C. A multi-process degradation was suggested by the differential scanning calorimetry evaluation and later confirmed by the use of the kinetic methods. The results were assessed using the preliminary ASTM E698 method, by means of which an apparent activation energy (Ea) value of 112.1 kJ min−1 was calculated. The implementation of the isoconversional Friedman differential method and Flynn–Wall–Ozawa integral method revealed a dependence of the Ea value to the conversion degree and an indication of a multistage decomposition responsible for the thermal degradation of the drug. As such, the nonparametric kinetics method was applied and a three-process degradation was revealed, all processes being determined by both physical transformations and chemical reactions.

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Acknowledgements

This work was funded and completely supported by the infrastructure of West University of Timisoara, postdoctoral advanced research Grant no. 3869/0-1/26.01.2022 (The modulation and optimization of the physicochemical and biopharmaceutical profile of some atypical antidepressants).

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Authors and Affiliations

  1. Faculty of Chemistry, Biology, Geography, West University of Timisoara, 16 Pestalozzi Street, 300115, Timişoara, Romania

    Denisa Circioban, Titus Vlase & Gabriela Vlase

  2. Faculty of Pharmacy, Advanced Instrumental Screening Center, University of Medicine and Pharmacy “Victor Babeş”, 2Nd Eftimie Murgu Square, 300041, Timişoara, Romania

    Ionuţ Ledeţi & Adriana Ledeţi

  3. Department of Applied Chemistry, Organic and Natural Compounds Engineering, Politehnica University of Timișoara, 6 Carol Telbisz, 300001, Timişoara, Romania

    Gerlinde Rusu

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  1. Denisa Circioban
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  4. Gerlinde Rusu
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Contributions

Conceptualization was contributed by DC, AL and GV; Data curation was contributed by DC, GR and GV; Formal analysis was contributed by DC, IL and TV; Funding acquisition was contributed by DC; Methodology was contributed by IL, TV and AL; Project administration was contributed by DC; Resources were contributed by DC and GV; Software was contributed by TV and AL; Validation was contributed by GV; Writing was contributed by DC, IL and AL. The agreement between the authors assumes that all authors have equal rights.

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Correspondence to Adriana Ledeţi.

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The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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Circioban, D., Ledeţi, I., Vlase, T. et al. Stability evaluation and kinetic study for the atypical antidepressant opipramol. J Therm Anal Calorim 148, 13121–13131 (2023). https://doi.org/10.1007/s10973-023-12249-3

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