Trimethoprim-Based multicomponent solid Systems: Mechanochemical Screening, characterization and antibacterial activity assessment.

In this work, multicomponent trimethoprim-based pharmaceutical solid systems were developed by mechanochemistry, using coformers from the GRAS list and other active pharmaceutical ingredients. The choice of coformers took into account their potential to increase the aqueous solubility/dissolution rate of TMP or its antibacterial activity. All the binary systems were characterized by thermal analysis, powder X-ray diffraction and infrared spectroscopy, and 3 equimolar systems with FTIR pointing to salts, and 4 eutectic mixtures were identified.

Norfloxacin Cocrystals: Mechanochemical Synthesis and Scale-up Viability Through Solubility Studies.

Cocrystals are recognized as one of the most efficient approaches to improve aqueous solubility of Biopharmaceutical Classification System, BCS, classes II and IV drugs. Cocrystal discovery and the establishment of experimental conditions suitable for scale-up purposes are some of the main challenges in cocrystal investigation. In this work, the investigation of mechanochemical synthesis of norfloxacin cocrystals with picolinic and isonicotinic acids is performed, leading to the discovery of two new cocrystals of this important BCS class IV antibiotic, which were characterized through thermal, spectral and diffractometric analysis.

Dihydrofolate Reductase Inhibitors: The Pharmacophore as a Guide for Co-Crystal Screening.

In this work, co-crystal screening was carried out for two important dihydrofolate reductase (DHFR) inhibitors, trimethoprim (TMP) and pyrimethamine (PMA), and for 2,4-diaminopyrimidine (DAP), which is the pharmacophore of these active pharmaceutical ingredients (API). The isomeric pyridinecarboxamides and two xanthines, theophylline (THEO) and caffeine (CAF), were used as co-formers in the same experimental conditions, in order to evaluate the potential for the pharmacophore to be used as a guide in the screening process. In silico co-crystal screening was carried out using BIOVIA COSMOquick and experimental screening was performed by mechanochemistry and supported by (solid + liquid) binary phase diagrams, infrared spectroscopy (FTIR) and X-ray powder diffraction (XRPD).