Department of Biotechnology, Yuanpei University, Hsin Chu, Taiwan, ROC.
Adv Drug Deliv Rev. 2012 Apr;64(5):461-78. doi: 10.1016/j.addr.2012.01.009. Epub 2012 Jan 24.
The solid-state chemistry of drugs has seen growing importance in the pharmaceutical industry for the development of useful API (active pharmaceutical ingredients) of drugs and stable dosage forms. The stability of drugs in various solid dosage forms is an important issue because solid dosage forms are the most common pharmaceutical formulation in clinical use. In solid-state stability studies of drugs, an ideal accelerated method must not only be selected by different complicated methods, but must also detect the formation of degraded product. In this review article, an analytical technique combining differential scanning calorimetry and Fourier-transform infrared (DSC-FTIR) microspectroscopy simulates the accelerated stability test, and simultaneously detects the decomposed products in real time. The pharmaceutical dipeptides aspartame hemihydrate, lisinopril dihydrate, and enalapril maleate either with or without Eudragit E were used as testing examples. This one-step simultaneous DSC-FTIR technique for real-time detection of diketopiperazine (DKP) directly evidenced the dehydration process and DKP formation as an impurity common in pharmaceutical dipeptides. DKP formation in various dipeptides determined by different analytical methods had been collected and compiled. Although many analytical methods have been applied, the combined DSC-FTIR technique is an easy and fast analytical method which not only can simulate the accelerated drug stability testing but also at the same time enable to explore phase transformation as well as degradation due to thermal-related reactions. This technique offers quick and proper interpretations.
药物的固态化学在制药工业中变得越来越重要，因为它可以开发出有用的药物活性成分（API）和稳定的剂型。各种固体制剂中药物的稳定性是一个重要问题，因为固体制剂是临床使用最常见的药物制剂形式。在药物的固态稳定性研究中，理想的加速方法不仅必须通过不同的复杂方法进行选择，还必须检测降解产物的形成。在这篇综述文章中，结合差示扫描量热法和傅里叶变换红外（DSC-FTIR）微光谱分析技术模拟了加速稳定性试验，并实时检测分解产物。以药用二肽天冬甜精半水合物、赖诺普利二水合物和依那普利马来酸盐为测试实例，这些二肽要么与 Eudragit E 一起，要么不与 Eudragit E 一起。这种一步法同时 DSC-FTIR 实时检测二酮哌嗪（DKP）的技术直接证明了脱水过程和作为药物二肽中常见杂质的 DKP 形成。通过不同的分析方法确定了各种二肽中的 DKP 形成情况，并进行了收集和汇编。尽管已经应用了许多分析方法，但结合 DSC-FTIR 技术是一种简单快速的分析方法，不仅可以模拟药物的加速稳定性测试，还可以同时探索由于热相关反应而导致的相转变和降解。该技术提供了快速准确的解释。
