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

Abstract

The co-crystallization of active pharmaceutical ingredients (APIs) has received increasing attention due to the modulation of the relative physicochemical properties of APIs such as low solubility, weak permeability and relatively inferior oral bioavailability. Crystal engineering plays a decisive role in the systematic design and synthesis of co-crystals by means of exerting control on the inter-molecular interactions. The characterization and detection of such co-crystal formations plays an essential role in the field of pharmaceutical research and development. In this work, nitrofurantoin (NF), melamine (MELA) and their hydrated co-crystal form were characterized and analyzed by using terahertz time-domain spectroscopy (THz-TDS) and Raman vibrational spectroscopy. According to the experimental THz spectra, the hydrated co-crystal form has characteristic absorption peaks at 0.67, 1.05, 1.50 and 1.73 THz, while the THz spectra for the two raw parent materials (NF and MELA) are quite different within this spectral region. Similar observations were made from the experimental Raman vibrational spectra results. Density functional theory (DFT) calculation was performed to help determine the major vibrational modes of the hydrated co-crystal between nitrofurantoin and melamine, as well as identify the structural changes due to inter- and/or intra-molecular hydrogen bonding motifs between NF and MELA. The results of the theoretical frequency calculations corroborate the THz and Raman experimental spectra. The characteristic bands of the NF–MELA-hydrated co-crystal between nitrofurantoin and melamine were also determined based on the DFT simulated calculation. The reported results in this work provide us with a wealth of structural information and a unique vibrational spectroscopic method for characterizing the composition of specific co-crystals and inter-molecular hydrogen bonding interactions upon pharmaceutical co-crystallization.

The Necessity of Periodic Boundary Conditions for the Accurate Calculation of Crystalline Terahertz Spectra

“…95,96 However, many recent studies have used ab initio gas-phase simulations to assign experimental condensed phase terahertz spectra, with varying levels of apparent success. [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] It is important to note that in almost all of these cases the discussed 'agreement' with experiment is largely based upon the position of calculated vibrational transitions, with little focus placed upon the accuracy of the predicted mode-types -critical for gaining deeper insight into the way terahertz motions influence bulk material properties, for example. Therefore, this work aims to asses how gas-phase simulations reproduce terahertz spectra, as well as predicting the corresponding vibrational mode-types.…”

“…29 However, due to the complexity and (assumed) increased computational cost of periodic boundary condition simulations, gas-phase calculations involving clusters of molecules have been employed in studies describing terahertz vibrations, with varying levels of apparent success. [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] It is important to note that, in general, such assessment is based solely on the position of the calculated transitions, with little focus on the actual motions involved or their accuracy. However, there is a lack of comparison in the literature between these methods, and therefore this work aims to assess how gas-phase simulations perform in regard to reproducing not only the experimental terahertz spectra, but also the prediction of the vibrational mode-types.…”

In acid-aminopyrimidine continuum: experimental and computational studies of furan tetracarboxylate-2-aminopyrimidinium salt

“…All possible donor-acceptor interactions have been analysed using the theory of second order perturbations of the off-diagonal Fock matrix element between "lled" Lewis-type NBOs (donor) and "empty" non-Lewis NBOs (acceptor). 69,70 The intensity of interaction between NBO donors and NBO acceptors is well expressed by stabilization energy E (2) (kcal mol À1 ) (Table 4). The NBO parameters associated with the hydrogen bond interactions involving LP (Lone pair) / s* (anti-bonding) transition between 2-AP and FTCA have been studied by taking into…”

Terahertz and Raman Spectroscopic Investigation of Monohydrate Cocrystal of Antitubercular Isoniazid with Protocatechuic Acid

“…Compared with cocrystal, salt formation is limited to acid–base reaction. However, cocrystallization provides different avenues, where any pharmaceutical substance may form cocrystals without having ionizable groups [ 10 ]. Additionally, on the premise of almost no effect on the chemical structure, intrinsic biological activity and pharmacological activity of APIs [ 11 ], cocrystallization strategy can significantly optimize the physicochemical properties and clinical performance of specific APIs [ 12 , 13 ].…”