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.

Cocrystallization by the solvent drop grinding technique has been employed successfully to generate highly water-soluble cocrystals of a poorly soluble nutraceutical hesperetin with different coformers, picolinic acid, nicotinamide, and caffeine. The miniscule amount of solvent (ethanol here), added during grinding, expectedly imparts high molecular mobility and efficiency to the method. On the basis of preliminary indication of the phase transformation by differential scanning calorimetry, these cocrystals were further characterized by Fourier transform-infrared and solid state NMR spectroscopy. However, the final structural confirmation of these distinct cocrystalline forms was provided by either single crystal X-ray diffraction (XRD) for HESP-PICO or powder XRD data in Material Studio software to generate the crystal structure of HESP-NICO and HESP-CAFF. The data revealed the existence of supramolecular synthons established by novel hydrogen bonds between hydroxyl groups of hesperetin with acid or amide carbonyl (CO), and/or amidic NH 2 , and/or pyridine/aromatic nitrogen (N aromatic ) of coformers. Dissolution studies of cocrystals in aqueous buffer showed maximum concentration of hesperetin to be nearly 4−5 times higher than the pure substance. This has led to optimized pharmacokinetics as exhibited by improved relative bioavailability (HESP-PICO:1.36, HESP-NICO:1.57, HESP-CAFF:1.60). Furthermore, the enhanced antioxidant and antihemolytic effect, coupled with the protective action against inflammation, signifies the development of a clinically useful and a pharmaceutically acceptable form of hesperetin.

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The present study deals with the application of mechanochemical approach for the preparation of drug-drug multicomponent solid forms of three poorly soluble antihypertensive drugs (telmisartan, irbesartan and hydrochlorothiazide) using atenolol as a coformer. The resultant solid forms comprise of cocrystal (telmisartan-atenolol), coamorphous (irbesartan-atenolol) and eutectic (hydrochlorothiazide-atenolol). The study emphasizes that solid-state transformation of drug molecules into new forms is a result of the change in structural patterns, diminishing of dimers and creating new facile hydrogen bonding network based on structural resemblance. The propensity for heteromeric or homomeric interaction between two different drugs resulted into diverse solid forms (cocrystal/coamorphous/eutectics) and become one of the interesting aspects of this research work. Evaluation of these solid forms revealed an increase in solubility and dissolution leading to better antihypertensive activity in deoxycorticosterone acetate (DOCA) salt-induced animal model. Thus, development of these drug-drug multicomponent solid forms is a promising and viable approach to addressing the issue of poor solubility and could be of considerable interest in dual drug therapy for the treatment of hypertension.