Pharmaceutical Cocrystals of Diflunisal and Diclofenac with Theophylline

Pharmaceutical cocrystals of nonsteroidal anti-inflammatory drugs diflunisal (DIF) and diclofenac (DIC) with theophylline (THP) were obtained, and their crystal structures were determined. In both of the crystal structures, molecules form a hydrogen bonded supramolecular unit consisting of a centrosymmetric dimer of THP and two molecules of active pharmaceutical ingredient (API). Crystal lattice energy calculations showed that the packing energy gain of the [DIC + THP] cocrystal is derived mainly from the dispersion energy, which dominates the structures of the cocrystals. The enthalpies of cocrystal formation were estimated by solution calorimetry, and their thermal stability was studied by differential scanning calorimetry. The cocrystals showed an enhancement of apparent solubility compared to the corresponding pure APIs, while the intrinsic dissolution rates are comparable. Both cocrystals demonstrated physical stability upon storing at different relative humidity

Salicylamide Cocrystals: Screening, Crystal Structure, Sublimation Thermodynamics, Dissolution, and Solid-State DFT Calculations

A new cocrystal of 2-hydroxybenzamide (A) with 4-acetamidobenzoic acid (B) has been obtained by the DSC screening method. Thermophysical analysis of the aggregate [A:B] has been conducted and a fusion diagram has been plotted. Cocrystal formation from melts was studied by using thermomicroscopy. A cocrystal single-crystal was grown and its crystal structure was determined. The pattern of noncovalent interactions has been quantified using the solid-state DFT computations coupled with the Bader analysis of the periodic electron density. The sublimation processes of A-B cocrystal have been studied and its thermodynamic functions have been calculated. The classical method of substance transfer by inert gas-carrier was chosen to investigate sublimation processes experimentally. The lattice energy is found to be 143 ± 4 kJ/mol. It is lower than the sum of the corresponding values of the cocrystal pure components. The theoretical value of the lattice energy, 156 kJ/mol, is in reasonable agreement with the experimental one. A ternary phase diagram of solubility (A-B–ethanol) has been plotted and the areas with solutions for growing thermodynamically stable cocrystals have been determined

Fenamate Cocrystals with 4,4′-Bipyridine: Structural and Thermodynamic Aspects

Cocrystallization of nonsteroidal anti-inflammatory drug fenamates (<i>N</i>-phenylanthranilic acid (N-PA), niflumic acid0 (NFA), flufenamic acid (FFA), tolfenamic (TFA) and mefenamic acids (MFA)) with 4,4′-bipyridine (BP) has resulted in the formation of cocrystals with a 2:1 molar ratio. Crystal Packing Similarity analysis has revealed that the packing arrangement of the [N-PA+BP], [TFA+BP], and [MFA+BP] cocrystals consists of discrete fragments of the crystal structures of initial APIs connected to each other by BP molecules. In the case of [FFA+BP], the cocrystal contains a previously unseen packing arrangement of FFA molecules which may be a fragment of a new polymorphic FFA form. Differential scanning calorimetry studies show a good correlation between the cocrystal melting temperature and the melting points of the corresponding pure APIs. The enthalpies of cocrystal formation are small, which indicates that the packing energy gain only originates from weak van der Waals interactions between the API and BP molecules