Interconvertible Hydrochlorothiazide–Caffeine Multicomponent Pharmaceutical Materials: A Solvent Issue
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AuthorVerdugo-Escamilla, Cristóbal; Acebedo Martínez, Francisco Javier; Domínguez Martín, Alicia; Gómez Morales, Jaime; Choquesillo Lazarte, Duane
Verdugo-Escamilla, C.; Alarcón-Payer, C.; Frontera, A.; Acebedo-Martínez, F.J.; Domínguez-Martín, A.; Gómez-Morales, J.; Choquesillo-Lazarte, D. Interconvertible Hydrochlorothiazide–Caffeine Multicomponent Pharmaceutical Materials: A Solvent Issue. Crystals 2020, 10, 1088. https://doi.org/10.3390/cryst10121088
SponsorshipSpanish Agencia Estatal de Investigacion of the Ministerio de Ciencia, Innovacion y Universidades (MICIU); European Union (EU) PGC2018-102047-B-I00; MICIU/AEI from SPAIN CTQ2017-85821-R
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.