Raman and Terahertz Spectroscopic Investigation of Cocrystal Formation Involving Antibiotic Nitrofurantoin Drug and Coformer 4-aminobenzoic Acid

Abstract

Cocrystallizaiton could improve most physicochemical properties of specific active pharmaceutical ingredients, which has great potential in pharmaceutical development. In this study, the cocrystal of nitrofurantoin and 4-aminobenzoic acid was prepared with solid-state (solvent-free or green-chemistry) grinding approach, and the above cocrystal has been characterized by Raman and terahertz vibrational spectroscopic techniques. Spectral results show that the vibrational modes of the cocrystal within the whole spectral region are different from those of the corresponding parent materials. The dynamic process of such pharmaceutical cocrystal formation has also been monitored directly with Raman spectra. These results offer us unique means for characterizing the cocrystal conformation from molecule-level and also provide us rich information about the reaction dynamic of cocrystal formation within pharmaceutical fields.

Co-Crystal Formation of Antibiotic Nitrofurantoin Drug and Melamine Co-Former Based on a Vibrational Spectroscopic Study

“…Figure 3 shows the THz absorption spectra of NF, MELA and their hydrated co-crystal, ranging from 0.2 to 1.8 THz. NF shows two characteristic peaks at the positions 1.26 and 1.61 THz, which is consistent with the anhydrous form of NF reported in our previous work [ 22 ], while MELA does not have any obvious absorption peaks during this spectral range. However, the corresponding NF–MELA-hydrated co-crystal has four peaks at 0.67, 1.05, 1.50 and 1.73 THz, respectively, and this is quite different to the two starting parent materials shown in the THz spectra.…”

“…Therefore, the spectral features in the THz absorption spectra are usually considered to be dependent on intra- and/or inter-molecular behaviors including hydrogen bonding or other weak non-valence bonding interactions. In particular, it has potential applications in the pharmaceutical field for the analysis of crystalline compounds throughout the pharmaceutical development and research processes [ 22 ]. With the help of THz spectroscopic technology, it is possible to directly detect and differentiate different solid-state forms of APIs and their corresponding co-crystals, and to exploit structural change information for such specific pharmaceutical co-crystals whose crystal structures are stabilized by weak inter- and/or intra-molecular interactions between APIs and various CCFs [ 24 , 25 ].…”

“…The physicochemical properties of these co-crystals, such as the aqueous solubility and photo-stability, were enhanced significantly and their results suggested that co-crystallization could be a viable alternative for improving the biopharmaceutical properties of APIs. Du et al [ 22 ] investigated the structure and dynamic formation process of the NF-4-aminobenzoic acid co-crystal with typical vibrational spectroscopy, and the results indicated that the spectroscopic techniques could offer an attractive experimental method to identify and characterize pharmaceutical co-crystal formation and its dynamic process. Vibrational spectroscopic techniques include mid-infrared, Raman and terahertz (THz) spectroscopy, which have already been successfully used to explain co-crystallization of different solid-state pharmaceuticals [ 23 , 24 , 25 , 26 ].…”