01190nas a2200169 4500008004100000245010300041210006900144260000800213300001600221490000700237520057100244100002200815700002000837700002000857700002000877856012300897 2016 eng d00aCrystal engineering of a zwitterionic drug to neutral cocrystals: a general solution for floxacins0 aCrystal engineering of a zwitterionic drug to neutral cocrystals cSEP a12610-126130 v523 a

The transformation of zwitterionic Sparfloxacin (SPX) to the neutral form is achieved by cocrystallization. Neutral forms of drugs are important for higher membrane permeability, while zwitterions are more soluble in water. The twin advantages of higher solubility/dissolution rate and good stability of neutral SPX are achieved in a molecular cocrystal compared to its zwitterionic SPX hydrate. The amine-phenol supra-molecular synthon drives cocrystal formation, with the paraben ester acting as a "proton migrator'' for the ionic to neutral transformation.

1 aGunnam, Anilkumar1 aSuresh, Kuthuru1 aGanduri, Ramesh1 aNangia, Ashwini uhttps://library.ncl.res.in/content/crystal-engineering-zwitterionic-drug-neutral-cocrystals-general-solution-floxacins01944nas a2200241 4500008004100000022001400041245007900055210006900134260000800203300001400211490000700225520118000232100001801412700001701430700002401447700002201471700002101493700002201514700002001536700001801556700001901574856010901593 2019 eng d a1528-748300aCrystalline acylhydrazone photoswitches with multiple mechanical responses0 aCrystalline acylhydrazone photoswitches with multiple mechanical cMAY a3039-30440 v193 a

The advancement of our understanding of stimuli responsive molecular crystals has led to the realization that they hold great yet unexplored potential as adaptive materials. Although molecular crystals that exhibit a single mechanical response to a single input stimulus are now abundant, crystals that are capable of response to multiple stimuli are rather scarce. Here we report two photoswitchable acylhydrazone derivatives, Ac-1 and Ac-2, which respond to light as well as to mechanical force. Upon application of localized mechanical stress, the anhydrous (Ac-1a) and monohydrate (Ac-1h) crystals of Ac-1 undergo plastic shearing deformation and bending, whereas monohydrate crystals of Ac-2 undergo elastic deformation. When they are exposed to UV light, crystals of Ac-1h and Ac-2 undergo photoinduced bending; on the other hand, crystals of Ac-1a and thicker crystals of Ac-2 exhibit photosalient effect (light-induced leaping). It is demonstrated that the synergistic action of multiple stimuli (UV light and force) elicits enhanced mechanical response, and this strategy could be employed in the future to increase the efficacy of single crystal actuators.

1 aGupta, Poonam1 aPanda, Tamas1 aAllu, Suryanarayana1 aBorah, Silpisikha1 aBaishya, Anamika1 aGunnam, Anilkumar1 aNangia, Ashwini1 aNaumov, Pance1 aNath, Naba, K. uhttps://library.ncl.res.in/content/crystalline-acylhydrazone-photoswitches-multiple-mechanical-responses03041nas a2200193 4500008004100000245013000041210006900171260000900240300001400249490000700263520232300270100001902593700002202612700001902634700002002653700002002673700002402693856013002717 2023 eng d00aCocrystallization of multi-kinase inhibitor pazopanib with fenamic acids: improving dissolution and inhibiting cell migration0 aCocrystallization of multikinase inhibitor pazopanib with fenami cOCT  a5565-55740 v253 a

A multi-kinase inhibitor, pazopanib (PAZ) is cocrystallized with cyclooxygenase (COX) inhibitor fenamic acids to investigate the dissolution rate and inhibition of cell migration in VEGF-triggered HUVEC cells to test the efficacy of stoichiometric drug-drug combinations. Crystallization experiments at the sub-milligram level in an acetonitrile-methanol mixture yielded two drug-drug salt forms of PAZ with flufenamic acid (FFA) and niflumic acid (NFA) as PAZ+center dot FFA-center dot ACN (an acetonitrile solvate named as form I) and PAZ+center dot NFA-. Structures of the crystal forms were characterized by single crystal X-ray diffraction (SC-XRD) method. Crystal structures revealed that the presence of a 2-aminopyrimidine group in PAZ is a strong partner for the carboxyl group in all solid forms, forming an acidMIDLINE HORIZONTAL ELLIPSISpyrimidine heterosynthon with COX inhibitor fenamic acids. To perform dissolution experiments and cell line analysis, the scale-up of both salt forms were done in the acetonitrile-methanol mixture through crystallization, which showed a polymorphic transformation in the case of PAZ+center dot FFA-center dot ACN (an acetonitrile solvate named form II). The thermodynamic stability of PAZ+center dot FFA-center dot ACN (form II) and PAZ+center dot NFA- were analysed using slurry experiment under ambient conditions in pH 1.2 (0.1 N HCl) buffer medium and the residual solid phase was characterized by powder XRD, which showed that PAZ+center dot FFA-center dot ACN (form II) was a metastable solid form while PAZ+center dot NFA- was a stable solid form. The dissolution experiments at gastric pH 1.2 showed that the rate of dissolution of PAZ+center dot FFA-center dot ACN was 10 times higher than PAZ+center dot NFA-. The cell migration assay suggested that PAZ+center dot FFA-center dot ACN inhibited similar to 25% and PAZ+center dot NFA- inhibited similar to 20% migration of HUVEC cells compared to PAZ alone. These investigations suggested that the drug-drug salts PAZ+center dot FFA- and PAZ+center dot NFA- would be potential combo drug candidates for clinical trials. Multi-drug crystalline salts of pazopanib with fenamic acids exhibit enhanced dissolution and 20% higher inhibition in the migration of HUVEC cells compared to the reference drug.

1 aRai, Sunil, K.1 aGunnam, Anilkumar1 aRoy, Debopriya1 aRajput, Raveena1 aKulkarni, Kiran1 aNangia, Ashwini, K. uhttps://library.ncl.res.in/content/cocrystallization-multi-kinase-inhibitor-pazopanib-fenamic-acids-improving-dissolution-and