RT Journal Article
T1 Interconvertible Hydrochlorothiazide-Caffeine Multicomponent Pharmaceutical Materials: A Solvent Issue
A1 Verdugo-Escamilla, Cristobal
A1 Alarcon-Payer, Carolina
A1 Frontera, Antonio
A1 Javier Acebedo-Martinez, Francisco
A1 Dominguez-Martin, Alicia
A1 Gomez-Morales, Jaime
A1 Choquesillo-Lazarte, Duane
K1 cocrystal
K1 codrug
K1 hydrochlorothiazide
K1 caffeine
K1 mechanochemical synthesis
K1 Co-crystals
K1 Solubility
K1 Cocrystals
K1 Design
K1 Dissolution
K1 Synthon
K1 Program
AB 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 pi-pi stacking interactions.
PB Mdpi
SN 2073-4352
YR 2020
FD 2020-12-01
LK http://hdl.handle.net/10668/19255
UL http://hdl.handle.net/10668/19255
LA en
DS RISalud
RD Apr 6, 2025