Interconvertible Hydrochlorothiazide–Caffeine Multicomponent Pharmaceutical Materials: A Solvent Issue

Abstract

The design of new multicomponent pharmaceutical materials that involve different active pharmaceutical ingredients (APIs), e.g., drug-drug cocrystals, is a novel and interesting approach to address new therapeutic challenges. In this work, the hydrochlorothiazide-caffeine (HCT–CAF) codrug and its methanol solvate have been synthesized by mechanochemical methods and thoroughly characterized in the solid state by powder and single crystal X-ray diffraction, respectively, as well as differential scanning calorimetry, thermogravimetric analyses and infrared spectroscopy. In addition, solubility and stability studies have also been performed looking for improved physicochemical properties of the codrug. Interestingly, the two reported structures show great similarity, which allows conversion between them. The desolvated HCT–CAF cocrystal shows great stability at 24 h and an enhancement of solubility with respect to the reference HCT API. Furthermore, the contribution of intermolecular forces on the improved physicochemical properties was evaluated by computational methods showing strong and diverse H-bond and π–π stacking interactions.

Polymorphism in the 1/1 Pterostilbene/Picolinic Acid Cocrystal

“…This procedure and level of theory has been used before to investigate noncovalent interactions in the solid state. 17 The molecular electrostatic potential surfaces were computed at the same level and represented using a 0.001 au isosurface. The QTAIM analysis 18 and NCIplot index 19 calculations were computed at the same level of theory by means of the AIMAll program.…”

Weak Interactions in Cocrystals of Isoniazid with Glycolic and Mandelic Acids

“…For the former the BSSE correction [36] has been applied and for the latter we have used the kinetic energy density values at the bond critical points that emerge upon complexation, applying the methodology proposed by Espinosa et al [37]. This methodology has been recently used to evaluate non-covalent interactions in the solid state [38][39][40][41][42][43][44][45]. The NCI plot iso-surfaces [46,47] have been generated using the AIMAll program [35] using the PBE0-D3/def2-TZVP wavefunction.…”

1-Ethyluracil, a New Scaffold for Preparing Multicomponent Forms: Synthesis, Characterization, and Computational Studies

“…Since we intend to estimate the interactions in the solid state, the crystallographic coordinates have been used. This level of theory and methodology have previously been used to evaluate similar interactions. − In this work the binding energy and interaction energy terms have been used interchangeably. They were computed as the difference between the energies of the isolated monomers and their assembly and were corrected for the basis set superposition error (BSSE) by using the Boys–Bernardi counterpoise method .…”