Effects of Heat Treatment on Indomethacin-Cimetidine Mixture; Investigation of Drug-Drug Interaction Using Singular Value Decomposition in FTIR Spectroscopy
Effects of Heat Treatment on Indomethacin-Cimetidine Mixture; Investigation of Drug-Drug Interaction Using Singular Value Decomposition in FTIR Spectroscopy
复制标题
DOI：
10.1016/j.xphs.2020.09.049
复制
发表时间：
2021-02-15
影响因子：
3.8
通讯作者：
Goto, Satoru
中科院分区：
文献类型：
--
作者：
Otsuka, Yuta;Kuwashima, Wataru;Goto, Satoru
利用红外光谱和多因素分析研究了相变对吲哚美辛（IMC）、西咪替丁（CIM）及其1:1共晶混合物的影响。将IMC form gamma、CIM form A和IMC-CIM 1:1混合物摩尔比样品在303-453 K的热板上加热5 min，冷却至室温。用KBr粉末对制备的样品进行了粉末x射线衍射分析和红外光谱分析。PXRD图谱表明，块状IMC形态为gamma，块状CIM形态为A， 1:1物理混合样品分别相变为低结晶度IMC形态为gamma，无定形CIM和共晶混合物。FTIR光谱结合奇异值分解（SVD）分析了几种振动模式的吸光度和峰移，表明样品的多晶转变影响其分子相互作用。在SVD结果的基础上，用s型拟合方法估计了加热样品的熔点。SVD主成分分析表明，IMC-CIM 1:1混合试样的相变过程影响IMC的C=O拉伸、C-C拉伸和C- h弯曲的红外振动。这些结果表明，分子相互作用是影响IMC-CIM 1:1混合物共晶状态的重要因素。这一观察结果使我们能够评价非晶态制剂或多晶片剂中药物组合的稳定性。(C) 2020美国药剂师协会(R)。Elsevier Inc.出版。版权所有。
This study investigated the effect of phase transformation on indomethacin (IMC), cimetidine (CIM), and their 1:1 eutectic mixture, using FTIR spectra and multivariate analysis. The IMC form gamma, CIM form A, and IMC-CIM 1:1 mixture molar ratio samples were heated on a hot plate at 303-453 K for 5 min and cooled till room temperature. The prepared samples were investigated by powder X-ray diffraction analysis and infrared spectroscopy with KBr powder. The PXRD patterns suggested the bulk IMC form gamma, bulk CIM form A, and 1:1 physical mixture samples phase transformed into low-crystallinity IMC form gamma, amorphous CIM, and eutectic mixture, respectively. FTIR spectra combined with singular value decomposition (SVD) suggested by absorbance oopeak shifts of several vibration modes that the polymorphic transformations of the samples affect their molecular interactions. The estimated melting points of heated samples were evaluated by sigmoid fitting based on the SVD results. The principal components of SVD show that the process of phase transformation of IMC-CIM 1:1 mixture samples affect the IR vibration of the C=O stretch of IMC and the C-C stretch and C-H bending of CIM. These results suggest that molecular interaction is an important factor in the eutectic condition of IMC-CIM 1:1 mixture. This observation enables to evaluate for in co-amorphous formulations or stability of drug combinations in a poly pill. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.