The structure of the prepared MNZ–GA cocrystal is studied by means of molecular dynamics and density functional theory calculations, powder X-ray diffraction, infrared spectroscopy, and thermal analysis. A cocrystal of MNZ is prepared using gallic acid (GA) as cocrystal former. In the present study, the properties of MNZ were optimized through a cocrystallization strategy. Metronidazole (MNZ) is a water-soluble antimicrobial drug that can cause high plasma concentration peaks after administration, which may relate to serious encephalopathy. Pharmaceutical cocrystal as an alternative modification strategy presents opportunities for the formulation development of drugs with undesirable pharmacokinetic properties. Additionally, at the end of this paper, we collect a chronological survey of the most representative scientific papers reporting the mechanochemical synthesis of cocrystals. Hence, in this review, we describe and discuss the relevance of mechanochemical procedures in the formation of multicomponent solid forms focusing on pharmaceutical cocrystals. In this sense, we are interested in highlighting the advantages of mechanochemical methods on the obtaining of pharmaceutical cocrystals. These sustainable methods have had an enormous impact on a great variety of chemistry fields, including catalysis, organic synthesis, metal complexes formation, preparation of multicomponent pharmaceutical solid forms, etc.
Being able to substitute, in many cases, classical solution reactions often requiring significant amounts of solvents.
Inkdrop note taking met free#
Mechanochemistry is considered an alternative attractive greener approach to prepare diverse molecular compounds and has become an important synthetic tool in different fields (e.g., physics, chemistry, and material science) since is considered an ecofriendly procedure that can be carried out under solvent free conditions or in the presence of minimal quantities of solvent (catalytic amounts). The products formed from ink-jet printing show excellent consistency in the particle size distribution and can be easily subjected to scaling up in industry compared to those prepared using the conventional co-crystallization techniques such as slurry grinding, rotavapor and routine solution evaporation which are time consuming and produce varying particle sizes which is a hindrance to product development and scaling during mass production. Using the well-known thermal ink-jet printing (TIJP), organic solutions of metronidazole and substituted hydroxybenzoic acids were injected into a cartridge and printed onto the template via jet dispensing mechanism by varying the drug–coformer stoichiometric ratio to generate the cocrystals and eutectics of the adducts in quick time. In particular, the structures of the cocrystals were determined using single crystal X-ray diffraction whereas those of the eutectics were identified based on PXRD, DSC and binary phase diagram construction. The products have been characterized and analyzed using Powder X-Ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), Scanning Electron Microscope (SEM) and Thermogravimetric analysis (TGA). Co-crystallization experiments using liquid assisted grinding (LAG), melt cool and routine solvent evaporation yielded eutectics except for the combinations 3,5-dihydroxy and 3,4,5-trihydroxybenzoic acids which produce cocrystals. Co-crystallization of metronidazole, an antibiotic antiprotozoal drug, belonging to the family of nitro-imidazole, with benzoic acid and mono, di, tri hydroxybenzoic acids results in multi-component adducts with better physico-chemical properties than the drug. Multi-component adducts such as cocrystals and eutectics have become an integral part of pharmaceutical industry since the application potential of such products is imminent in drug design and fabrication.
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