The results of the sixth blind test of organic crystal structure prediction methods are presented and discussed, highlighting progress for salts, hydrates and bulky flexible molecules, as well as on-going challenges.

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This study highlights the improved biopharmaceutical properties of quercetin with therapeutically active coformers: picolinic acid and nicotinamide, using cocrystallization, well supported by antioxidant, antihaemolytic and pharmacokinetic activities.

The present study investigates the structural and pharmaceutical properties of different multicomponent crystalline forms of lamotrigine (LTG) with some pharmaceutically acceptable coformers viz. nicotinamide (1), acetamide (2), acetic acid (3), 4-hydroxy-benzoic acid (4) and saccharin (5). The structurally homogeneous phases were characterized in the solid state by DSC/TGA, FT-IR and XRD (powder and single crystal structure analysis) as well as in the solution phase. Forms 1 and 2 were found to be cocrystal hydrate and cocrystal, respectively, while in forms 3, 4 and 5, proton transfer was observed from coformer to drug. The enthalpy of formation of multicomponent crystals from their components was determined from the enthalpy of solution of the cocrystals and the components separately. Higher exothermic values of the enthalpy of formation for molecular complexes 3, 4 and 5 suggest these to be more stable than 1 and 2. The solubility was measured in water as well as in phosphate buffers of varying pH. The salt solvate 3 exhibited the highest solubility of the drug in water as well as in buffers over the pH range 7-3 while the cocrystal hydrate 1 showed the maximum solubility in a buffer of pH 2. A significant lowering of the dosage profile of LTG was observed for 1, 3 and 5 in the animal activity studies on mice.

The present study reports novel cocrystals of telmisartan (TEL) with saccharin and glutaric acid. Crystal engineering approaches such as solution crystallization, solid-state grinding and slurry method have been utilized with the ultimate objective of improving the solubility of this BCS class II drug. The physical characterization revealed that the cocrystals are unique vis-à-vis thermal, spectroscopic and X-ray diffraction properties. Structural characterization showed that the cocrystals with saccharin and glutaric acid exist in monoclinic P2 1 /c and triclinic P1 space groups, respectively. The improved solubility of telmisartansaccharin (TEL-SAC) (nine-fold) and telmisartan-glutaric acid (two-fold) cocrystals in comparison with the free drug has been demonstrated in solubility experiments in phosphate buffer, pH 7.5. The TEL-SAC cocrystal remained stable in the aqueous medium for 6 hours as confirmed by PXRD. The AUC 0-24 of TEL-SAC and TEL-GA was found to be 2-fold and 1.4-fold increased in terms of bioavailability than pure TEL, respectively. The in vivo antihypertensive activity of TEL-SAC in DOCA salt-induced hypertensive rats showed two-fold improved efficacy, while acute toxicity studies revealed no signs of toxicity in rats even at doses of 2000 mg kg −1 of body weight (BW). The new solid phase of telmisartan with saccharin represents a promising and viable opportunity for the manufacture of a drug product with improved therapeutic outcomes.