A series of olanzapine (OLN) dicarboxylic acid salts including earlier reports on olanzapinium malonate (1:1) and maleate (1:1 and 1:2) were prepared mechanochemically using liquid assisted grinding (LAG) in order to study their hydration stability. Powder Xray diffraction was used as a characterization tool during the investigation. On the basis of the single crystal structures of respective OLN salts, a negative correlation between the dicarboxylic acid chain length and the hydration stability of the corresponding OLN salt was found. Our observations suggest that the overall crystal packing, beyond the stronger hydrogen bond synthon () plays an important role in designing OLN salts with better hydration stability. In addition, melting point analysis showed that OLN dicarboxylic acid salts follow melting point alteration behavior similar to the pure diacids.

Drug–drug and drug–nutraceutical multicomponent solids of an antipsychotic drug olanzapine (OLN) are prepared using mechanochemistry.

Olanzapine (OLN), an antipsychotic drug of biopharmaceutical classification system (BCS) class II, has been studied extensively in the literature. A large number of solvates, stoichiometric hydrates, salts, cocrystals, and polymorphs were reported, categorized into four different packing types A, B, C, and D. Among them most of the solvated structures belong to type C packing, whereas other multicomponent structures show diversity in packing and are categorized into A, B, and D classes. Some of the reported salts (disalts) even show new packing types lacking the most common OLN dimer motif. Compared to other multicomponent systems, only a few OLN salts were reported. A scope is there to study the possible crystalline arrangement for this unexplored category with various salt formers such as glycolic acid (Gly), 4hydroxybenzoic acid (4HBA), 2,4-dihydroxybenzoic acid (24DHBA), 2,5dihydroxybenzoic acid (25DHBA), 2,6-dihydroxybenzoic acid (26DHBA), and p-toluenesulfonic acid (pTSA) containing available hydrogen bonding sites with positional variation. The highlight of this work is the DHBA salts that show a new packing arrangement (type E) whereas Gly, 4HBA, and pTSA salts belong to the reported categories.

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.

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