A 2 : 1 urea • adipic acid cocrystal was obtained in two polymorphic forms (Form I reported earlier, and Form II synthesized in this study) using mechanochemistry as well as solution crystallization. Lower solubility and leaching study showed the newly synthesized urea • adipic acid 2 : 1 cocrystal to be an efficient sustained-release nitrogen fertilizer compared to commercially available urea.
Five
cocrystals of antiviral drug favipiravir (Fav) with respiratory
drug theophylline (Theo) and GRAS coformers, viz., p-aminobenzoic acid (PABA), 4-hydroxybenzoic acid (4HBA), gallic acid
(GA), and ferulic acid (FRA), were successfully synthesized using
mechanochemistry as well as solution crystallization. All the synthesized
cocrystals were characterized using PXRD, SCXRD, and thermal analysis.
A physicochemical property investigation showed an excellent correlation
of coformer solubility with cocrystal solubility. Moreover, cocrystal
solubility can be tuned based on the selection of coformers during
cocrystallization as well as the pH of the medium. Crystal structure
analysis depicts amide–amide homosynthon formation in the Fav·Theo
cocrystal and an acid–amide heterosynthon in the case of cocrystals
with GRAS coformers. Incorporation of nutraceuticals (GA and FRA)
provides an additional health benefit, whereas Fav·Theo cocrystal
may be a potential formulation to treat patients suffering from chronic
obstructive pulmonary disease (COPD) or asthma along with viral infections.
Olanzapine (OLN), an antipsychotic drug, is one of the most widely studied pharmaceutical materials. Although OLN and most of their multicomponent solids are highly crystalline, some of their molecular salts are difficult to crystallize and optimization takes a long time. After several batches of failed crystallization, we applied mechanochemistry and microcrystal electron diffraction (MicroED) for structure elucidation. This combined approach was successful not only in structure determination of the drug molecule but also in characterizing traces of impurity present in a bulk solid. This study demonstrates that the combined approach is fast and efficient for structure elucidation of pharmaceutical materials when generation of suitable single crystals is challenging.
Olanzapine (OLN), an anti-psychotic drug, is one of the most widely studied pharmaceutical materials. Although OLN and most of their multicomponent solids are highly crystalline, some of their molecular salts are difficult to crystallize and optimization takes long time. After several batches of failed crystallization, we applied mechanochemistry and microcrystal electron diffraction (MicroED) for structure elucidation. This combined approach was successful not only in structure determination of the drug molecule but also in characterizing traces of impurity present in a bulk solid. This study demonstrates that the combined approach is fast and efficient for structure elucidation of pharmaceutical materials when generation of suitable single crystals is challenging.
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