Department of Medicinal Chemistry, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland.
Department of Biophysics, Faculty of Medicine, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland.
Molecules. 2022 Jul 3;27(13):4283. doi: 10.3390/molecules27134283.
Pharmaceutical excipients should not interact with active substances, however, in practice, they sometimes do it, affecting the efficacy, stability and safety of drugs. Thus, interactions between active substances and excipients are not desirable. For this reason, two component mixtures of oral antidiabetic drug linagliptin (LINA) with four excipients of different reactivity, i.e., lactose (LAC), mannitol (MAN), magnesium stearate (MGS) and polyvinylpyrrolidone (PVP), were prepared in a solid state. A high temperature and a high humidity of 60 °C and 70% RH, respectively, were applied as stressors in order to accelerate the potential interactions between LINA and excipients. Differential scanning calorimetry (DSC) as well as Fourier transform infrared (FT-IR) and near infrared (NIR) spectroscopy were used to estimate the changes due to potential interactions. In addition, chemometric computation of the data with principal component analysis (PCA) and hierarchical cluster analysis (HCA) was applied to adequately interpret the findings. Of the excipients used in the present experiment, all of them were not inert in relation to LINA. Some of the interactions were shown without any stressing, whereas others were observed under high-temperature/high-humidity conditions. Thus, it could be concluded that selection of appropriate excipients for LINA is very important question to minimize its degradation, especially when new types of formulations with LINA are being developed and manufactured.
药用辅料不应与活性物质相互作用，但在实践中，它们有时会相互作用，从而影响药物的疗效、稳定性和安全性。因此，不希望活性物质与辅料之间发生相互作用。出于这个原因，将口服抗糖尿病药物利那列汀（LINA）与四种反应性不同的赋形剂（乳糖（LAC）、甘露醇（MAN）、硬脂酸镁（MGS）和聚乙烯吡咯烷酮（PVP））制备成固体混合物。分别采用高温（60°C）和高湿度（70%相对湿度）作为应激剂，以加速 LINA 和赋形剂之间潜在的相互作用。采用差示扫描量热法（DSC）以及傅里叶变换红外（FT-IR）和近红外（NIR）光谱法来评估潜在相互作用引起的变化。此外，还应用主成分分析（PCA）和层次聚类分析（HCA）对数据进行化学计量学计算，以充分解释研究结果。在本实验中使用的赋形剂中，没有一种对 LINA 是惰性的。有些相互作用在没有任何应激的情况下表现出来，而另一些则在高温/高湿条件下观察到。因此，可以得出结论，选择合适的 LINA 赋形剂对于最小化其降解非常重要，特别是在开发和制造新型 LINA 制剂时。
