Purpose

This study aimed to develop evaluation methods for multicomponent system interactions between drug excipients of three active pharmaceutical ingredients, namely, monoammonium glycyrrhizinate (MAG), glycine (Gly) and DL-methionine (Met), by using thermal and non-thermal techniques.

Methods

Simultaneous thermal (TGA/DTG-DSC) analytical techniques, isothermal stress testing-high-performance liquid chromatography (IST-HPLC), scanning electron microscopy (SEM), and X-ray powder diffraction (XRPD) were used to investigate the characterization and potential physical and chemical interactions.

Results

Based on the TGA/DTG-DSC results, the three drugs could maintain thermal stability at temperatures below 150 °C and were compatible with microcrystalline cellulose (MCC), calcium carboxymethylcellulose (CC), hydroxypropyl methyl cellulose (HPMC), low-substituted hydroxypropyl cellulose (L-HPC), magnesium stearate (MS), and poly(vinylpyrrolidone) (PVP). MAG, Gly and Met had physicochemical incompatibilities with lactose monohydrate (LM) based on thermal investigations, which was confirmed using IST-HPLC experiments. XRPD analysis indicated that crystalline transformation did not occur among all drug-excipient mixtures.

Conclusion

TGA/DTG-DSC is a suitable and simple method for the detection of potential incompatibilities between drugs and excipients, especially for multicomponent formulations. These results can be used as a reference for the development of multicomponent glycyrrhizin (GL) solid dosage forms.

中文翻译：

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通过热和非热技术对复方甘草甜素固体制剂的三种活性药物成分的物理化学表征和相容性分析

目的

本研究旨在通过热和非热技术开发评估三种活性药物成分（即甘草酸单铵（MAG）、甘氨酸（Gly）和DL-蛋氨酸（Met））的药物辅料之间的多组分系统相互作用的方法。

方法

同步热 (TGA/DTG-DSC) 分析技术、等温应力测试-高效液相色谱 (IST-HPLC)、扫描电子显微镜 (SEM) 和 X 射线粉末衍射 (XRPD) 用于研究表征和潜在的物理和化学相互作用。

结果

TGA/DTG-DSC结果表明，3种药物在150℃以下均能保持热稳定性，并与微晶纤维素（MCC）、羧甲基纤维素钙（CC）、羟丙基甲基纤维素（HPMC）、低取代羟丙基纤维素 (L-HPC)、硬脂酸镁 (MS) 和聚乙烯吡咯烷酮 (PVP)。基于热研究，MAG、Gly 和 Met 与一水乳糖 (LM) 存在物理化学不相容性，这已通过 IST-HPLC 实验得到证实。XRPD 分析表明在所有药物-赋形剂混合物中都没有发生结晶转变。

结论

TGA/DTG-DSC 是检测药物和辅料之间潜在不相容性的合适且简单的方法，特别是对于多组分制剂。这些结果可作为多组分甘草甜素（GL）固体剂型开发的参考。