Thermal stability, preformulation, and kinetic degradation studies for gestrinone

IF 3 3区 工程技术 Q2 CHEMISTRY, ANALYTICAL
Amalia Ridichie, Cosmina Bengescu, Adriana Ledeţi, Gerlinde Rusu, Răzvan Bertici, Titus Vlase, Gabriela Vlase, Francisc Peter, Ionuţ Ledeţi, Matilda Rădulescu
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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.

Abstract Image

孕诺酮的热稳定性、预配制和动力学降解研究
雌孕酮是一种用于治疗子宫内膜异位症的活性药物成分,以胶囊剂的形式使用,目前正在对阴道内给药进行评估,同时还对其潜在的抗肿瘤作用进行了研究。本研究的目的是确定孕三烯酮与用于开发固体药物制剂的四种辅料(一水α-乳糖、硬脂酸镁、淀粉和滑石粉)的相容性,并借助动力学分析获得孕三烯酮的全面热分析特征曲线。在环境条件下,利用 ATR-FTIR 光谱研究,通过仪器筛选,对孕甾酮和每种赋形剂之间的 1:1 质量/质量二元混合物进行了制剂前研究,随后研究了热处理(TG/DTG/DSC)对样品的影响。所得结果表明,在环境条件下,活性药物成分与所选辅料之间不会发生化学作用,而在热应力条件下,所有体系都会出现不相容现象。根据 ASTM E698 标准对分解机理进行了初步评估,随后根据弗里德曼、基辛格-阿卡希拉-苏诺塞和弗林-沃尔-奥泽的等转化法完成了评估。研究的最后一部分采用改进的 NPK 方法阐明了分解机理。这种方法表明,孕三烯酮的热降解是由两个单独的过程造成的,这两个过程都由叠加的物理变化和化学降解组成。
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来源期刊
CiteScore
8.50
自引率
9.10%
发文量
577
审稿时长
3.8 months
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.
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