{"title":"Thermal stability, preformulation, and kinetic degradation studies for gestrinone","authors":"Amalia Ridichie, Cosmina Bengescu, Adriana Ledeţi, Gerlinde Rusu, Răzvan Bertici, Titus Vlase, Gabriela Vlase, Francisc Peter, Ionuţ Ledeţi, Matilda Rădulescu","doi":"10.1007/s10973-024-13520-x","DOIUrl":null,"url":null,"abstract":"<p>Gestrinone is an active pharmaceutical ingredient used in the treatment of endometriosis as capsules, with ongoing evaluation for intravaginal administration, while also having been studied for its potential antitumoral effects. The purpose of this study was to determine the compatibility of gestrinone with four excipients used in the development of solid pharmaceutical formulations (α-lactose monohydrate, magnesium stearate, starch, and talc) and to obtain a fully characterized thermoanalytical profile of gestrinone with the help of kinetic analysis. Preformulation studies were carried out on 1:1 mass/mass binary mixtures between gestrinone and each excipient by instrumental screening under ambient conditions using ATR-FTIR spectroscopy investigations, and later by studying the effect of thermal treatment over the samples (TG/DTG/DSC). The obtained results suggest that under ambient conditions, no chemical interactions take place between the active pharmaceutical ingredient and selected excipients, whereas under thermal stress incompatibilities are observed in all systems. The mechanism of decomposition was preliminary evaluated by the ASTM E698 and later completed by the isoconversional methods of Friedman, Kissinger–Akahira–Sunose, and Flynn–Wall–Ozawa, which suggest similar mean activation energies. The mechanism of decomposition was elucidated in the last part of the study, by employing the modified NPK method. This method suggests that gestrinone is thermally degraded by the contribution of two individual processes, both consisting of superimposed physical transformations and chemical degradations.</p>","PeriodicalId":678,"journal":{"name":"Journal of Thermal Analysis and Calorimetry","volume":"13 1","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Thermal Analysis and Calorimetry","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1007/s10973-024-13520-x","RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Gestrinone is an active pharmaceutical ingredient used in the treatment of endometriosis as capsules, with ongoing evaluation for intravaginal administration, while also having been studied for its potential antitumoral effects. The purpose of this study was to determine the compatibility of gestrinone with four excipients used in the development of solid pharmaceutical formulations (α-lactose monohydrate, magnesium stearate, starch, and talc) and to obtain a fully characterized thermoanalytical profile of gestrinone with the help of kinetic analysis. Preformulation studies were carried out on 1:1 mass/mass binary mixtures between gestrinone and each excipient by instrumental screening under ambient conditions using ATR-FTIR spectroscopy investigations, and later by studying the effect of thermal treatment over the samples (TG/DTG/DSC). The obtained results suggest that under ambient conditions, no chemical interactions take place between the active pharmaceutical ingredient and selected excipients, whereas under thermal stress incompatibilities are observed in all systems. The mechanism of decomposition was preliminary evaluated by the ASTM E698 and later completed by the isoconversional methods of Friedman, Kissinger–Akahira–Sunose, and Flynn–Wall–Ozawa, which suggest similar mean activation energies. The mechanism of decomposition was elucidated in the last part of the study, by employing the modified NPK method. This method suggests that gestrinone is thermally degraded by the contribution of two individual processes, both consisting of superimposed physical transformations and chemical degradations.
期刊介绍:
Journal of Thermal Analysis and Calorimetry is a fully peer reviewed journal publishing high quality papers covering all aspects of thermal analysis, calorimetry, and experimental thermodynamics. The journal publishes regular and special issues in twelve issues every year. The following types of papers are published: Original Research Papers, Short Communications, Reviews, Modern Instruments, Events and Book reviews.
The subjects covered are: thermogravimetry, derivative thermogravimetry, differential thermal analysis, thermodilatometry, differential scanning calorimetry of all types, non-scanning calorimetry of all types, thermometry, evolved gas analysis, thermomechanical analysis, emanation thermal analysis, thermal conductivity, multiple techniques, and miscellaneous thermal methods (including the combination of the thermal method with various instrumental techniques), theory and instrumentation for thermal analysis and calorimetry.