DSC, FTIR and Raman Spectroscopy Coupled with Multivariate Analysis in a Study of Co-Crystals of Pharmaceutical Interest

Abstract

Co-crystals have garnered increasing interest in recent years as a beneficial approach to improving the solubility of poorly water soluble active pharmaceutical ingredients (APIs). However, their preparation is a challenge that requires a simple approach towards co-crystal detection. The objective of this work was, therefore, to verify to what extent a multivariate statistical approach such as principal component analysis (PCA) and cluster analysis (CA) can be used as a supporting tool for detecting co-crystal formation. As model samples, physical mixtures and co-crystals of indomethacin with saccharin and furosemide with p-aminobenzoic acid were prepared at API/co-former molar ratios 1:1, 2:1 and 1:2. Data acquired from DSC curves and FTIR and Raman spectroscopies were used for CA and PCA calculations. The results obtained revealed that the application of physical mixtures as reference samples allows a deeper insight into co-crystallization than is possible with the use of API and co-former or API and co-former with physical mixtures. Thus, multivariate matrix for PCA and CA calculations consisting of physical mixtures and potential co-crystals could be considered as the most profitable and reliable way to reflect changes in samples after co-crystallization. Moreover, complementary interpretation of results obtained using DSC, FTIR and Raman techniques is most beneficial.

Salt Cocrystal of Diclofenac Sodium-L-Proline: Structural, Pseudopolymorphism, and Pharmaceutics Performance Study

“…The other changes revealed were the shifting of the C=O band at 1573 cm −1 to 1585 cm −1 and the amino stretching band from 1400 cm −1 to 1411 cm −1 . This data reflected the alteration of COO − vibration of NDH and amino sidechains of LP [ 21 , 37 , 38 ]. A sharp band on 1334 cm −1 also supported the data of new interaction that involved –OH and C–O carboxylic.…”

“…In the crystal arrangement, FTIR has commonly used to detect the hydrogen bonding formation [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. Figure 3 a reveals infrared spectra of NDH, LP, physical mixture 1:1 (PM), and NDP crystals from ethanol, methanol, and acetone, respectively.…”

“…Due to some overlapped bands, the second derivative spectra ( Figure 3 b) was generated to increase specificity by separating the overlapped bands on the similar region [ 37 , 38 ]. There are three focused areas shown in Figure 3 , with the distinctive bands assigned by the wavenumber point and arrow.…”

“…The functional group’s broadband at 3200–3750 cm −1 region also may involve –NH and NH–O stretching. Meanwhile, 1600-1750 cm −1 included –NH bend and –C=O stretching of carboxylic from both starting materials of the intermolecular bond [ 21 , 26 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ].…”

“…Data were processed by Microsoft Excel 2003 and Origin-Pro 8.5.1 software. The second derivative spectra were generated to enhance the specificity [ 37 , 38 ].…”