02437nas a2200277 4500008004100000022001400041245017600055210006900231260006700300300001000367490000700377520139300384653001801777653001401795653002201809653003201831653002101863653002101884653001701905653002601922100002301948700001701971700002401988700002702012856012002039 2014 eng d a0108-270100aCorrelation of the solid-state reactivities of racemic 2,4(6)-di-O-benzoyl-myo-inositol 1,3,5-orthoformate and its 4,4 `-bipyridine cocrystal with their crystal structures0 aCorrelation of the solidstate reactivities of racemic 246diObenz a111 RIVER ST, HOBOKEN 07030-5774, NJ USAbWILEY-BLACKWELLcNOV a1040+0 v703 a

Racemic 2,4(6)-di-O-benzoyl-myo-inositol 1,3,5-orthoformate, C21H18O8, (1), shows a very efficient intermolecular benzoyl-group migration reaction in its crystals. However, the presence of 4,4 `-bipyridine molecules in its cocrystal, C21H18O8 center dot C10H8N2, (1)center dot BP, inhibits the intermolecular benzoyl-group transfer reaction. In (1), molecules are assembled around the crystallographic twofold screw axis (b axis) to form a helical self-assembly through conventional O-H center dot center dot center dot O hydrogen-bonding interactions. This helical association places the reactive C6-O-benzoyl group (electrophile, El) and the C4-hydroxy group (nucleophile, Nu) in proximity, with a preorganized El center dot center dot center dot Nu geometry favourable for the acyl transfer reaction. In the cocrystal (1)center dot BP, the dibenzoate and bipyridine molecules are arranged alternately through OH center dot center dot center dot N interactions. The presence of the bipyridine molecules perturbs the regular helical assembly of the dibenzoate molecules and thus restricts the solid-state reactivity. Hence, unlike the parent dibenzoate crystals, the cocrystals do not exhibit benzoyl-transfer reactions. This approach is useful for increasing the stability of small molecules in the crystalline state and could find application in the design of functional solids.

10aacyl transfer10acocrystal10acrystal structure10adesign of functional solids10ahelical assembly10ahydrogen bonding10amyo-inositol10asolid-state reactions1 aTamboli, Majid, I.1 aBahadur, Vir1 aGonnade, Rajesh, G.1 aShashidhar, Mysore, S. uhttps://library.ncl.res.in/content/correlation-solid-state-reactivities-racemic-246-di-o-benzoyl-myo-inositol-135-004390nas a2200265 4500008004100000022001400041245017900055210006900234260007400303300001400377490000700391520332100398653003003719653004303749653001403792653002203806653002103828653002603849653002303875653002803898100002503926700002403951700002403975856012503999 2015 eng d a2053-229600aCrystal structures of the pyrazinamide-p-aminobenzoic acid (1/1) cocrystal and the transamidation reaction product 4-(pyrazine-2-carboxamido)-benzoic acid in the molten state0 aCrystal structures of the pyrazinamidepaminobenzoic acid 11 cocr a2 ABBEY SQ, CHESTER, CH1 2HU, ENGLANDbINT UNION CRYSTALLOGRAPHYcNOV a1010-U2760 v713 a

The synthesis of pharmaceutical cocrystals is a strategy to enhance the performance of active pharmaceutical ingredients (APIs) without affecting their therapeutic efficiency. The 1: 1 pharmaceutical cocrystal of the antituberculosis drug pyrazinamide (PZA) and the cocrystal former p-aminobenzoic acid (p-ABA), C7H7NO2- C5H5N3O, (1), was synthesized successfully and characterized by relevant solid-state characterization methods. The cocrystal crystallizes in the monoclinic space group P21/n containing one molecule of each component. Both molecules associate via intermolecular O-H center dot center dot center dot O and NH center dot center dot center dot O hydrogen bonds [O center dot center dot center dot O = 2.6102 (15)angstrom and O-H center dot center dot center dot O = 168.3 (19)degrees; N center dot center dot center dot O = 2.9259 (18) angstrom and N-H center dot center dot center dot O = 167.7 (16)degrees] to generate a dimeric acidamide synthon. Neighbouring dimers are linked centrosymmetrically through N-H center dot center dot center dot O interactions [N center dot center dot center dot O = 3.1201 (18) angstrom and N-H center dot center dot center dot O = 136.9 (14)degrees] to form a tetrameric assembly supplemented by C-H center dot center dot center dot N interactions [C center dot center dot center dot N = 3.5277 (19) angstrom and C-H center dot center dot center dot N = 147 degrees]. Linking of these tetrameric assemblies through N-H center dot center dot center dot O [N center dot center dot center dot O = 3.3026 (19) angstrom and N-H center dot center dot center dot O = 143.1 (17)degrees], NH center dot center dot center dot N [N center dot center dot center dot N = 3.221 (2) angstrom and N-H center dot center dot center dot N = 177.9 (17)degrees] and C-H center dot center dot center dot O [C center dot center dot center dot O = 3.5354 (18) angstrom and C-H center dot center dot center dot O = 152 degrees] interactions creates the twodimensional packing. Recrystallization of the cocrystals from the molten state revealed the formation of 4-(pyrazine-2-carboxamido) benzoic acid, C12H9N3O3, (2), through a transamidation reaction between PZA and p-ABA. Carboxamide (2) crystallizes in the triclinic space group P1 with one molecule in the asymmetric unit. Molecules of (2) form a centrosymmetric dimeric homosynthon through an acid-acid O-H center dot center dot center dot O hydrogen bond [O center dot center dot center dot O = 2.666 (3) angstrom and O-H center dot center dot center dot O = 178 (4) degrees]. Neighbouring assemblies are connected centrosymmetrically via a C-H center dot center dot center dot N interaction [C center dot center dot center dot N = 3.365 (3) angstrom and C-H center dot center dot center dot N = 142 degrees] engaging the pyrazine groups to generate a linear chain. Adjacent chains are connected loosely via C-H center dot center dot center dot O interactions [C center dot center dot center dot O = 3.212 (3) angstrom and CH center dot center dot center dot O = 149 degrees] to generate a two-dimensional sheet structure. Closely associated two-dimensional sheets in both compounds are stacked via aromatic pi-stacking interactions engaging the pyrazine and benzene rings to create a threedimensional multi-stack structure.

10aacid-amide hetero-synthon10aactive pharmaceutical ingredient (API)10acocrystal10acrystal structure10ahydrogen bonding10amolten-state reaction10apowder diffraction10atransamidation reaction1 aThorat, Shridhar, H.1 aSahu, Sanjay, Kumar1 aGonnade, Rajesh, G. uhttps://library.ncl.res.in/content/crystal-structures-pyrazinamide-p-aminobenzoic-acid-11-cocrystal-and-transamidation-102742nas a2200241 4500008004100000022001400041245010300055210006900158260000800227300001200235490000700247520195100254653001202205653002002217653001402237653001802251653002102269100002302290700002102313700002402334700001902358856012302377 2026 eng d a0724-874100aNovel cocrystal of quercetagetin: in vitro and in vivo insights into biopharmaceutical performance0 aNovel cocrystal of quercetagetin in vitro and in vivo insights i cMAR a927-9390 v433 a

Purpose Quercetagetin (QTGN) is a naturally occurring flavonol predominantly sourced from marigold flowers and possesses notable therapeutic potential, including antidiabetic, anticancer, antioxidant, anti-inflammatory, and antiviral properties. However, poor aqueous solubility and in turn bioavailability restrict therapeutic utility of QTGN. Crystal engineering is one of the approaches proven to be fruitful in resolving the solubility issues of many active pharmaceutical ingredients (APIs). Method In the present work, a cocrystal of QTGN using betaine (BET) as coformer viz. Quercetagetin & sdot;betaine & sdot;ethanol (QTGN & sdot;BET & sdot;EtOH) was synthesized using the solvent evaporation method. It was further characterized using Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Thermogravimetric analysis (TGA), Powder X-ray diffraction (PXRD), and single crystal XRD (SCXRD). Result FTIR studies confirmed hydrogen bonding between QTGN and BET. PXRD studies showed formation of new crystalline phase. The prepared cocrystal had stoichiometric ratio of 1:1:1 between QTGN, BET, and ethanol forming cocrystal ethanolate and shared robust hydroxyl & ctdot;carboxylate supramolecular synthon as confirmed by TGA and SCXRD, respectively. Equilibrium solubility study and in vitro dissolution study showed a significant improvement (p < 0.0001) in aqueous solubility of QTGN upon its cocrystallization with BET. Furthermore, in vivo pharmacokinetic study revealed a 1.28-fold increase in bioavailability of QTGN when formulated as cocrystal solvate. The prepared cocrystal was found to be stable over a period of six months at 40 degrees C and 75% RH when analyzed using PXRD studies. Conclusion The current work represents a frontier in pharmaceutical formulation, providing a means to fully harness the therapeutic potential of QTGN using cocrystal approach.

10abetaine10aBioavailability10acocrystal10aquercetagetin10aUSP apparatus IV1 aSuryawanshi, Smita1 aShaligram, Parth1 aGonnade, Rajesh, G.1 aPatil, Sharvil uhttps://library.ncl.res.in/content/novel-cocrystal-quercetagetin-vitro-and-vivo-insights-biopharmaceutical-performance