00686nas a2200181 4500008004100000022001400041245006200055210006200117260000800179300000900187490000700196653012600203100002400329700001800353700001900371700002000390856009400410 2014 eng d a2053-273300aSupramolecular synthon hierarchy in bumetanide cocrystals0 aSupramolecular synthon hierarchy in bumetanide cocrystals cFEB aC7210 v7010aNovel cocrystals of sulfonamide drug Bumetanide with carboxamides are developed based on supramolecular synthons approach1 aAllu, Suryanarayana1 aBolla, Geetha1 aTothadi, Srinu1 aNangia, Ashwini uhttps://library.ncl.res.in/content/supramolecular-synthon-hierarchy-bumetanide-cocrystals01861nas a2200169 4500008004100000245007400041210006900115260000800184300001400192490000700206520129100213100002401504700001801528700001901546700002001565856010601585 2017 eng d00aSupramolecular synthons in bumetanide cocrystals and ternary products0 aSupramolecular synthons in bumetanide cocrystals and ternary pro cAUG a4225-42360 v173 aA novel design strategy for cocrystals of the diuretic sulfonamide drug bumetanide (BUM) with carboxamides is reported based on reliable supramolecular synthons. Binary cocrystals of BUM with pyridine carboxamides, pyridones, and cytosine were obtained by solvent assisted grinding followed by solution crystallization. All cocrystal structures exhibit hydrogen bonding of the coformer with the carboxylic acid group of BUM via heterosynthons which replace the acid homodimer in the drug crystal structure. Pyridones are inserted as N-H center dot center dot center dot O dimers which are in turn bonded to the acid group of BUM, while the pyridine amide coformers interact via the acid amide heterosynthon. Cocrystal polymorphs were obtained for bumetanide isonicotinamide cocrystal structure with the sulfonamide pyridine and sulfonamide acid synthons. Careful crystal packing analysis of BUM structure and nine new binary adducts gave an idea for the design ternary cocrystals, and subsequently four new ternary crystalline products were crystallized. Whereas the binary cocrystal structures were confirmed by single crystal diffraction, the ternary combinations were chatacterized by their unique powder X-ray diffraction patterns as well as by thermal and spectroscopic techniques.1 aAllu, Suryanarayana1 aBolla, Geetha1 aTothadi, Srinu1 aNangia, Ashwini uhttps://library.ncl.res.in/content/supramolecular-synthons-bumetanide-cocrystals-and-ternary-products01944nas 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-responses01119nas a2200193 4500008004100000022001400041245009400055210006900149260000900218300001400227490000700241520045000248100002400698700002000722700001800742700002800760700002000788856011700808 2019 eng d a1466-803300aRole of hydrogen bonding in cocrystals and coamorphous solids: indapamide as a case study0 aRole of hydrogen bonding in cocrystals and coamorphous solids in cAPR  a2043-20480 v213 a

The stronger sulfonamide-pyridine (SO2NH2 center dot center dot center dot N-Py) and sulfonamide-carboxamide (SO2NH2 center dot center dot center dot O = C-NH) hydrogen bonds direct the formation of cocrystals, while the weaker sulfonamide-amine (SO2NH2 center dot center dot center dot N-H) hydrogen bond results in coamorphous products. IDP-PIP and IDP-ARG coamorphous solids exhibit remarkable stability under accelerated conditions.

1 aAllu, Suryanarayana1 aSuresh, Kuthuru1 aBolla, Geetha1 aMannava, M., K. Chaitan1 aNangia, Ashwini uhttps://library.ncl.res.in/content/role-hydrogen-bonding-cocrystals-and-coamorphous-solids-indapamide-case-study01824nas a2200181 4500008004100000022001400041245006000055210006000115260000800175300001200183490000700195520126300202100002401465700001801489700001901507700002401526856009201550 2020 eng d a1528-748300aNovel pharmaceutical cocrystals and salts of bumetanide0 aNovel pharmaceutical cocrystals and salts of bumetanide cFEB a793-8030 v203 a

New crystalline forms of bumetanide, namely, four cocrystals, two salts, and one salt-cocrystal were crystallized. Urea and lactams such as valerolactam, caprolactam, and N-methyl caprolactam formed cocrystals with bumetanide, whereas 4-aminopyridine gave a salt. Piperazine afforded a salt hydrate, and 5-fluorocytosine gave a salt-cocrystal. The supramolecular synthons in bumetanide-lactam cocrystals are an amide dimer between drug and coformer, and acid homo dimer between bumetanide molecules. In bumetanide salts, the acid proton is transferred from bumetanide to coformer amine, whereas in bumetanide salt-cocrystal proton transfer and free acid were observed in the crystal structure. Similarly, the cytosine salt-cocrystal of bumetanide and fluorocytosine also gave a salt-cocrystal adduct. The acid proton of bumetanide is transferred to the 2-amino pyridine base of cytosine as a salt, and on the other side of the drug molecule the sulfonamide interacts with the syn amide part of cytosine. Furthermore, solubility, dissolution, and diffusion membrane permeability experiments were performed on all new solid forms. The piperazine salt shows high dissolution and permeability crossover when compared to other binary forms of bumetanide.

1 aAllu, Suryanarayana1 aBolla, Geetha1 aTothadi, Srinu1 aNangia, Ashwini, K. uhttps://library.ncl.res.in/content/novel-pharmaceutical-cocrystals-and-salts-bumetanide01117nas a2200169 4500008004100000022001400041245009200055210006900147260000900216300001400225490000700239520051600246100001900762700002400781700002400805856011800829 2020 eng d a1528-748300aSalts and cocrystal of etodolac: advantage of solubility, dissolution, and permeability0 aSalts and cocrystal of etodolac advantage of solubility dissolut cJUL  a4512-45220 v203 a

{Etodolac (ETD) is a nonsteroidal anti-inflammatory drug (NSAID) approved by the United States Food and Drug Administration (US-FDA) in 1991 for the treatment of rheumatoid arthritis. Because of its poor aqueous solubility and high permeability, ETD falls under Biopharmaceutics Classification System (BCS) Class II drug. The present study was aimed to screen stable salts and cocrystals of ETD using Generally Recognized as Safe (GRAS) and a few non-GRAS coformers. Crystallization of five salts (i.e.

1 aRai, Sunil, K.1 aAllu, Suryanarayana1 aNangia, Ashwini, K. uhttps://library.ncl.res.in/content/salts-and-cocrystal-etodolac-advantage-solubility-dissolution-and-permeability01942nas a2200229 4500008004100000245009800041210006900139260000900208300001200217490000700229520115200236100002501388700002201413700002201435700002401457700002201481700002201503700002301525700002401548700002401572856011601596 2022 eng d00aThe effects of cis and trans butenedioic acid on the physicochemical behavior of lumefantrine0 aeffects of cis and trans butenedioic acid on the physicochemical cJAN  a156-1680 v243 aThe present work investigates the effects of cis and trans butenedioic acid isomers (maleic acid and fumaric acid) on the crystallinity and pharmaceutical behavior of lumefantrine. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), attenuated total reflectance infrared spectroscopy (ATR-IR), solid-state nuclear magnetic resonance spectroscopy (ss-NMR), and single-crystal X-ray diffraction (SC-XRD) studies were employed. Lumefantrine-fumaric acid crystallized as a salt in the monoclinic space group P2(1)/c. In comparison, DSC and PXRD showed the formation of a co-amorphous solid with maleic acid. Complete proton transfer with a strong ionic interaction led to crystalline salt formation with the trans isomer, whereas weaker/fewer hydrogen bonds with the cis isomer of butenedioic acid led to a co-amorphous salt. The in vitro dissolution of both salts resulted in a similar 2.6-2.7-fold improvement in dissolution rate when compared to that of the crystalline lumefantrine. The crystalline and co-amorphous salts were stable under accelerated stability conditions (40 +/- 2 degrees C and 75 +/- 5% RH) for one month.1 aTomar, Devendrasingh1 aLodagekar, Anurag1 aGunnam, Anilkumar1 aAllu, Suryanarayana1 aChavan, Rahul, B.1 aTharkar, Minakshi1 aAjithkumar, T., G.1 aNangia, Ashwini, K.1 aShastri, Nalini, R. uhttps://library.ncl.res.in/content/effects-cis-and-trans-butenedioic-acid-physicochemical-behavior-lumefantrine02461nas a2200169 4500008004100000245011900041210006900160260000800229300001600237490000700253520180700260100002402067700001902091700002902110700002402139856012802163 2022 eng d00aSynthesis of ternary cocrystals, salts, and hydrates of acefylline with enhanced dissolution and high permeability0 aSynthesis of ternary cocrystals salts and hydrates of acefylline cJUN a4165–41810 v223 a

Acefylline (ACF) is a stimulant xanthine derivative drug, which is formulated as a piperazine salt for the treatment of bronchial asthma. ACF falls under BCS class IV category of low solubility and poor permeability, which together limit the bioavailability and efficacy of the drug. In this work, ACF binary and ternary cocrystals, salts–cocrystals, and their polymorphs are synthesized by cocrystallization with several coformers. Two different methods were adopted for the supramolecular assembly of the ternary systems A.B.C: (1) first, binary adducts A.B or A.C were crystallized by grinding a slurry of the components in a suitable solvent and then C was added and grinding was continued; and (2) all three components were taken in a solvent slurry and ground together. The former method was found to be superior in affording the ternary salt/cocrystal. The role of laboratory seeding is implicated to explain the variation in crystallization results at different stages of the project. Crystal structures of the product’s binary and ternary systems were solved by single-crystal X-ray diffraction and powder X-ray diffraction data for structure solution. The crystal structures show the recurrence of carboxylate–pyridinium and imidazole–acid heterosynthons in the binary and ternary adducts. The intermolecular interactions between ACF and the coformer are analyzed by Hirshfeld surfaces, 2D fingerprint plots, and an energy framework. The permeability of ACF increases in binary and ternary systems with selected coformers. The fast dissolution and high permeability of ACF-PIP make this salt an improved crystalline formulation of acefylline.

1 aAllu, Suryanarayana1 aGarai, Abhijit1 aChernyshev, Vladimir, V.1 aNangia, Ashwini, K. uhttps://library.ncl.res.in/content/synthesis-ternary-cocrystals-salts-and-hydrates-acefylline-enhanced-dissolution-and-high02023nas a2200193 4500008004100000022001400041245010300055210006900158260000900227300001600236490000600252520133000258100001901588700002201607700002201629700002401651700002401675856013001699 2023 eng d a2470-134300aDabrafenib-panobinostat salt: improving the dissolution rate and inhibition of BRAF melanoma cells0 aDabrafenibpanobinostat salt improving the dissolution rate and i cMAY  a18255-182650 v83 a

Cocrystallization of the drug-drug salt-cocrystal of the histone deacetylase inhibitor (HDACi) panobinostat (PAN) and b-rapidly accelerated fibrosarcoma (BRAF) inhibitor dabrafenib (DBF) afforded single crystals of a two-drug salt stabilized by N+-H center dot center dot center dot O and N+-H center dot center dot center dot N- hydrogen bonds between the ionized panobinostat ammonium donor and dabrafenib sulfonamide anion acceptor in a 12-member ring motif. A faster dissolution rate for both drugs was achieved through the salt combination compared to the individual drugs in an aqueous acidic medium. The dissolution rate exhibited a peak concentration (Cmax) of approximately 310 mg cm-2 min-1 for PAN and 240 mg cm-2 min-1 for DBF at a Tmax of less than 20 min under gastric pH 1.2 (0.1 N HCl) compared to the pure drug dissolution values of 10 and 80 mg cm-2 min-1, respectively. The novel and fast-dissolving salt DBF-center dot PAN+ was analyzed in BRAFV600E melanoma cells Sk-Mel28. DBF-center dot PAN+ reduced the dose-response from micromolar to nanomolar concentrations and lowered IC50 (21.9 +/- 7.2 nM) by half compared to PAN alone (45.3 +/- 12.0 nM). The enhanced dissolution and lower survival rate of melanoma cells show the potential of novel DBF-center dot PAN+ salt in clinical evaluation.

1 aRai, Sunil, K.1 aMarverti, Gaetano1 aGunnam, Anilkumar1 aAllu, Suryanarayana1 aNangia, Ashwini, K. uhttps://library.ncl.res.in/content/dabrafenib-panobinostat-salt-improving-dissolution-rate-and-inhibition-braf-melanoma-cells