@misc{10481/66592,
year = {2020},
url = {http://hdl.handle.net/10481/66592},
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.},
organization = {Spanish Agencia Estatal de Investigacion of the Ministerio de Ciencia, Innovacion y Universidades (MICIU)},
organization = {European Union (EU)

PGC2018-102047-B-I00},
organization = {MICIU/AEI from SPAIN 	
CTQ2017-85821-R},
publisher = {MDPI},
keywords = {Cocrystal},
keywords = {Codrug},
keywords = {Hydrochlorothiazide},
keywords = {Caffeine},
keywords = {Mechanochemical synthesis},
title = {Interconvertible Hydrochlorothiazide–Caffeine Multicomponent Pharmaceutical Materials: A Solvent Issue},
doi = {10.3390/cryst10121088},
author = {Verdugo-Escamilla, Cristóbal and Acebedo Martínez, Francisco Javier and Domínguez Martín, Alicia and Gómez Morales, Jaime and Choquesillo Lazarte, Duane},
}