10567nas a2200205 4500008004100000245015900041210006900200260000800269490000700277520974600284100002110030700002410051700002410075700002310099700003310122700003210155700002410187700002310211856012710234 2020 eng d00aSynthesis, crystal structure and Hirshfeld surface analysis of the hydrated form of N’, N-(1,4-phenylenebis(methanylylidene) di(iso-nicotinic hydrazide)0 aSynthesis crystal structure and Hirshfeld surface analysis of th cAUG0 v283 a

The title compound, C20H16N6O2 was synthesized by reflux with isonicotinic hydrazide and terephthaldehyde in ethanol solvent with the acidic condition. The single-crystal X-ray structure determination of the title compound, N, N-(1,4-phenylene bis (methanylylidene) di(iso-nicotinic hydrazide), reveals that the molecule crystallizes in center of symmetry with water molecules (Dihydrated form, C20H16N6O2.2H2O) through N-H∙∙∙O and C-H∙∙∙O hydrogen bondings. Further, the crystal structure is stabilized by O-H∙∙∙O and weak C-H∙∙∙N hydrogen bondings with the formation of infinite chain and dimer. Further, surface analysis and fingerprint plot reveal that the significant hydrogen bonding such as H•••O (15.9%) and N•••H (11.4%) interactions play the most crucial role for its molecular packing.

1 aIngle, Kapil, S.1 aMohurle, Smital, A.1 aBairagi, Keshab, M.1 aShaikh, Tabrez, R.1 aVenugopala, Katharigatta, N.1 aChandrashekharappa, Sandeep1 aGonnade, Rajesh, G.1 aNayak, Susanta, K. uhttp://library.ncl.res.in/content/synthesis-crystal-structure-and-hirshfeld-surface-analysis-hydrated-form-n%E2%80%99-n-1402012nas a2200229 4500008004100000245011400041210006900155260000800224300001400232490000700246520121200253100002301465700002401488700002101512700001901533700001701552700001901569700002101588700002401609700002401633856012501657 2022 eng d00aNovel crystal forms of Entresto: a supramolecular complex of trisodium sacubitril/valsartan hemi-pentahydrate0 aNovel crystal forms of Entresto a supramolecular complex of tris cOCT a7387-73930 v243 a

Entresto is a salt-cocrystal supramolecular complex with the chemical name trisodium sacubitril/valsartan hemi-pentahydrate for treating chronic heart failure and was approved by the US FDA in 2015. This multidrug complex was synthesized in our laboratory to investigate its polymorphic behavior. Different crystallization conditions, including various solvent systems, yielded different novel solid forms of Entresto (Form-I to Form-VI), including the reported form. All the novel solids are solvent-dependent and were reproducibly crystallized on a 10 g scale quantity. The 1H NMR spectra confirmed the 1 : 1 stoichiometry of the two drugs, namely, sacubitril and valsartan, in all the solid forms of the crystalline products. Powder X-ray diffraction and DSC analysis of the crystalline solids established that they are distinct crystalline forms. Stability studies under ambient conditions carried out over a one-year period showed higher stability for Form-I and Form-III compared to the other forms, including the innovator crystal form (labelled as Form-II). The novel crystal forms (notably Form-I and Form-III) exhibit higher stability and less hygroscopicity than the reported Form-II.

1 aShaikh, Tabrez, R.1 aGeorge, Christy, P.1 aBhukya, Priyanka1 aShelke, Nikita1 aPawar, Komal1 aGarai, Abhijit1 aDandela, Rambabu1 aGonnade, Rajesh, G.1 aNangia, Ashwini, K. uhttp://library.ncl.res.in/content/novel-crystal-forms-entresto-supramolecular-complex-trisodium-sacubitrilvalsartan-hemi