02175nas a2200205 4500008004100000022001400041245006500055210006300120260007100183300001400254490000700268520145700275100002601732700002301758700002501781700002001806700002101826700002401847856009801871 2016 eng d a1528-748300aSyringic acid: structural elucidation and co-crystallization0 aSyringic acid structural elucidation and cocrystallization a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcAUG a4679-46870 v163 a

Syringic acid (SYRA) is a potential antioxidant used in traditional Chinese medicine and is an emerging nutraceutical. Current reports claim its potential anti-angiogenic, anti-glycating, anti-hyperglycaemic, neuroprotective, and memory-enhancing properties in various animal models. To date, SYRA crystal structure has not been elucidated, and no crystal engineering studies have been reported. This study reports the crystal structure of SYRA for the first time along with its nicotinamide (SNCT-E) and urea (SU-EA-M) co-crystals. All forms were successfully characterized using single crystal X-ray diffraction (XRD), powder XRD, and differential scanning calorimetry. Single crystal analysis revealed that SYRA crystallized in the C2/c space group, whereas SNCT-E (2:1) and SU-EA-M (1:2) crystallized in the P21/n and Cmca space group, respectively. Novel co-crystals have shown improved solubility, modified dissolution profiles, and improved flow and compressibility. Cytotoxic effects were explored in DU145 prostate cancer cell lines for the first time, and significant enhancement in cytotoxicity by the co-crystals was observed compared to plain components. A two-fold increase in % cytotoxicity of SNCT-E was observed when compared to the corresponding physical mixture. These studies shed light on potential utility of SYRA as a coformer for various pharmaceutical applications to design synergistic and organ-protective co-crystals.

1 aThipparaboina, Rajesh1 aMittapalli, Sudhir1 aThatikonda, Sowjanya1 aNangia, Ashwini1 aNaidu, V., G. M.1 aShastri, Nalini, R. uhttp://library.ncl.res.in/content/syringic-acid-structural-elucidation-and-co-crystallization03010nas a2200277 4500008004100000022001400041245007900055210006900134260000800203300001200211490000800223520215300231653002002384653002202404653000802426653001602434653001502450100001802465700002602483700002202509700002202531700002302553700002002576700002402596856011202620 2018 eng d a0731-708500aRufinamide: crystal structure elucidation and solid state characterization0 aRufinamide crystal structure elucidation and solid state charact cFEB a185-1920 v1493 a

Rufinamide (R) is a triazole derivative approved for the management of partial seizures and seizures associated with Lennox-Gastaut Syndrome, in November 2007. Crystal structure, solid state characterization, drug-excipient compatibility and solubility play a pivotal role in formulation development. This work deals with the crystal structure elucidation of R by single crystal X-ray diffraction and solid state characterization by thermal, spectroscopic and crystallographic techniques. Drug- excipient compatibility was assessed by differential scanning calorimetry (DSC). New RP-HPLC method for quantification of R was developed with improved retention time. Solubility and dissolution of drug in different media was determined. Additionally, the flow behavior of the drug was evaluated by measuring Carr's index and Hausner's ratio, while the compressibility behavior was studied using Well's protocol. R crystallized from dimethylformamide (R-DMF) was utilized for single crystal analysis. The drug crystallized in triclinic crystal system with P-1 space group. Asymmetric unit cell consists of two molecules of R held by intermolecular hydrogen bond (connected by N-H center dot center dot center dot O, which forms the catemeric chain). Analytical outcomes from DSC, thermogravimetric analysis (TGA) and powder X-ray diffraction (PXRD) revealed that the drug was present in pure crystalline form and was devoid of any polymorphic or pseudopolymorphic impurities. Influence of pH on the solubility and dissolution of R-DMF was found to be insignificant. The drug exhibited poor aqueous solubility, which was improved nearly 4.6 fold with the addition of 2% sodium lauryl sulphate (SLS). The drug exhibits poor flow and elastic compression nature. Excipients such as poly ethylene glycol (PEG) 8000, SLS, lactose monohydrate, starch and Hydroxypropyl methylcellulose (HPMC) E15 were incompatible with R-DMF as identified by thermal analysis. It is envisaged that these information regarding solid state properties of R-DMF would aid in identifying a logical path for formulation development. (C) 2017 Elsevier B.V. All rights reserved.

10aCompressibility10aDissolution media10aDSC10aHPLC method10asolubility1 aSalunke, Nita1 aThipparaboina, Rajesh1 aChavan, Rahul, B.1 aLodagekar, Anurag1 aMittapalli, Sudhir1 aNangia, Ashwini1 aShastri, Nalini, R. uhttp://library.ncl.res.in/content/rufinamide-crystal-structure-elucidation-and-solid-state-characterization02160nas a2200193 4500008004100000245010900041210006900150260000800219490000800227520145000235100002201685700002201707700002801729700001901757700001901776700002401795700002401819856012301843 2019 eng d00aCo amorphous valsartan nifedipine system: Preparation, characterization, in vitro and in vivo evaluation0 aCo amorphous valsartan nifedipine system Preparation characteriz cNOV0 v1393 a

Co amorphous systems are supersaturated drug delivery systems which offer a basic platform for delivery of multicomponent adducts (combination of more than one active pharmaceutical ingredient (API)) and/or as a fixed dose combination therapy, in addition to their potential to improve the apparent solubility, dissolution rate and ultimately bioavailability of poorly water soluble APIs. In the present work, a new drug-drug co amorphous system namely valsartan-nifedipine was prepared by quench cooling technique. Prepared co amorphous system was characterized for its solid state behavior with the help of Fourier Transform Infrared spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and Powder X Ray Diffractometry (PXRD). The optimized co amorphous system was stable for 1 month when exposed to accelerated stability condition (40 +/- 2 degrees C and 75 +/- 5% RH). The improved stability of amorphous nifedipine in co amorphous system was attributed to improved miscibility and intra and intermolecular non-covalent interactions mainly due to presence of hydrogen bonding between valsartan and nifedipine which was studied by FTIR analysis. Co amorphous systems were evaluated by mainly in vitro dissolution and in vivo benefit. In vitro dissolution study showed nearly 5.66 folds and 1.61 folds improvement which was translated to 3.63 and 2.19 times enhancement in vivo C-max for nifedipine and valsartan respectively.

1 aLodagekar, Anurag1 aChavan, Rahul, B.1 aMannava, M., K. Chaitan1 aYadav, Balvant1 aChella, Naveen1 aNangia, Ashwini, K.1 aShastri, Nalini, R. uhttp://library.ncl.res.in/content/co-amorphous-valsartan-nifedipine-system-preparation-characterization-vitro-and-vivo02216nas a2200181 4500008004100000245011400041210006900155260000800224300001400232490000700246520154700253100001901800700002201819700002601841700002401867700002401891856011901915 2019 eng d00aHepatoprotective cocrystals of isoniazid: synthesis, solid state characterization, and hepatotoxicity studies0 aHepatoprotective cocrystals of isoniazid synthesis solid state c cSEP a5161-51720 v193 a

Isoniazid (INH) is one of the first line drugs used in combination with pyrazinamide and rifampicin for the management of tuberculosis. Idiosyncratic hepatotoxicity is one of the most common side effects of antitubercular therapy worldwide. The current study explores solid phase modification of INH by cocrystallization with various hepatoprotective coformers, namely chrysin, hesperetin, silibinin, syringic acid (SYRA), and quercetin (QUE) to address hepatotoxicity concerns. Cocrystals were obtained with SYRA and QUE. Supramolecular synthons based on pyridine-carboxyl and pyridine-hydroxyl synthon enabled the formation of cocrystals. INHSYRA and INHQUE cocrystals were characterized by FT-IR, DSC, and PXRD. Single crystal X-ray analysis of INHSYRA revealed that it crystallized in triclinic system with the P (1) over bar space group. Intrinsic dissolution rate studies (IDR) showed slow drug release from both the cocrystals. Hepatoprotective effects of INHSYRA and INHQUE cocrystals were evaluated by a single toxic dose study and a subchronic study for 28 days. Results from the subchronic study indicated significant increase in ALT, AST, and ALP enzyme levels in the INH-treated group whereas the enzyme levels in INHSYRA and INHQUE cocrystal treated group were comparable to that of the untreated group. This study demonstrates the in vivo hepatoprotective effects of coformers SYRA and QUE provide promising evidence for utility of nutraceutical based coformers, to tackle hepatotoxicity associated with various drugs.

1 aYadav, Balvant1 aGunnam, Anilkumar1 aThipparaboina, Rajesh1 aNangia, Ashwini, K.1 aShastri, Nalini, R. uhttp://library.ncl.res.in/content/hepatoprotective-cocrystals-isoniazid-synthesis-solid-state-characterization-and02635nas a2200265 4500008004100000022001400041245012500055210006900180260000900249300001200258490000800270520175800278653001702036653001602053653000802069653000802077653002702085653001702112100002102129700002202150700002802172700002002200700002402220856012502244 2019 eng d a0039-914000aQuantification of niclosamide polymorphic forms - a comparative study by Raman, NIR and MIR using chemometric techniques0 aQuantification of niclosamide polymorphic forms a comparative st cJUL  a679-6880 v1993 a

Niclosamide, an anthelmintic drug recently repurposed for its activity against cancer, crystallizes into three solvated forms, two monohydrates (NHa, NHb) and one anhydrous (NAn) form. NAn is sensitive to pseudopolymorphic transformations that affect its dissolution and consequently, its bioavailability. NAn exhibits a polymorphic conversion to metastable monohydrate (NHa) form during high-energy milling in presence of poorly soluble solvents like water. It is hence very important to quantify polymorphic conversion from NAn to NHa, as water is a commonly used solvent during various processing like ball milling and wet granulation. This main objective of the study was to examine the feasibility of Raman, NIR and MIR spectroscopic techniques for identification and quantification of polymorphic forms of niclosamide in binary mixtures and multicomponent mixtures. Calibration models were developed and validated by vibrational spectroscopic techniques in binary mixtures of NAn and NHa and in multicomponent mixtures by chemometric techniques. These techniques were further used to identify and quantify NHa during ball milling, granulation and in presence of other polymorphic forms of niclosamide. Identification and quantification of pseudopolymorphs in binary and multicomponent mixtures with an acceptable recovery of 100.13-102.99% for Raman and 100.07-101.28% for NIR with low % RSD of 2.38-3.12 for both techniques were obtained. The % NHa determined during ball milling and granulation was similar by NIR and Raman. Raman spectroscopy however showed a greater advantage over other techniques in determining the NHa in presence of NHb due to significant difference in the spectral region of hydrates, when compared to NIR and MIR.

10aBall milling10aGranulation10aMSC10aPLS10aPolymorphic conversion10aspectroscopy1 aBhavana, Valmala1 aChavan, Rahul, B.1 aMannava, M., K. Chaitan1 aNangia, Ashwini1 aShastri, Nalini, R. uhttp://library.ncl.res.in/content/quantification-niclosamide-polymorphic-forms-comparative-study-raman-nir-and-mir-using01200nas a2200193 4500008004100000022001400041245009700055210006900152260000900221300001400230490000700244520052300251100001900774700002200793700001900815700002400834700002400858856012400882 2020 eng d a1528-748300aGeneration and evaluation of pharmacologically relevant drug-drug cocrystal for gout therapy0 aGeneration and evaluation of pharmacologically relevant drugdrug cJUN  a3577-35830 v203 a

The present study reports a novel drug-drug cocrystal of febuxostat and piroxicam for the treatment of gout. Single crystal X-ray diffraction revealed a monoclinic system with P2(1)/c space group. The prepared cocrystal enhanced the solubility of febuxostat and piroxicam and improved the dissolution rate of piroxicam in pH 6.8 as compared to the pure drug. Further, the compressibility assessment of cocrystal by Aulton and Wells method confirmed its plastic behavior and suitability for direct compression.

1 aModani, Sheela1 aGunnam, Anilkumar1 aYadav, Balvant1 aNangia, Ashwini, K.1 aShastri, Nalini, R. uhttp://library.ncl.res.in/content/generation-and-evaluation-pharmacologically-relevant-drug-drug-cocrystal-gout-therapy02109nas a2200205 4500008004100000022001400041245010300055210006900158260000900227300001200236490000700248520138000255100002801635700002201663700002201685700002401707700002401731700001901755856012901774 2021 eng d a1466-803300aEnhanced solubility, permeability, and tabletability of nicorandil by salt and cocrystal formation0 aEnhanced solubility permeability and tabletability of nicorandil cJAN  a227-2370 v233 a

Cocrystallization is a rational selection crystal engineering approach for the development of novel solid forms with enhanced physicochemical and mechanical properties. Nicorandil (NCR) is a niacinamide vitamin derivative used to treat angina pectoris. A binary solid form screen of NCR with homologous dicarboxylic acids afforded NCR-oxalic acid (NCR-OA, 1:1), NCR-fumaric acid (NCR-FA, 1:1), NCR-succinic acid (NCR-SA, 1:1), and NCR-suberic acid (NCR-SBA, 1:0.5). The binary solids were characterized by powder X-ray diffraction, IR and NMR spectroscopy, and DSC. NCR-FA and NCR-SBA were crystallized by slow evaporation from chloroform and toluene solvents, respectively. Single crystal X-ray diffraction confirmed that NCR-FA is a molecular salt, while NCR-SBA is a neutral cocrystal. NCR and the FA anion are connected via the robust carbovlate-pyridinium synthon, whereas in the NCR-SBA cocrystal, the components associate via the carboxylic acid- -pyridine synthon. The phase stability, solubility, dissolution rate, diffusion rate and tabletability studies have demonstrated that the binary solids exhibit improved physical and mechanical properties compared to the NCR drug. Specifically, the NCR-FA salt and NCR-SBA cocrystal have higher solubility, dissolution rate, and hardness at lower pressures, making the formulation suitable for tablet compression.

1 aMannava, M., K. Chaitan1 aGunnam, Anilkumar1 aLodagekar, Anurag1 aShastri, Nalini, R.1 aNangia, Ashwini, K.1 aSolomon, Anand uhttp://library.ncl.res.in/content/enhanced-solubility-permeability-and-tabletability-nicorandil-salt-and-cocrystal-formation01941nas a2200229 4500008004100000245009800041210006900139260000900208300001200217490000700229520115200236100002501388700002201413700002201435700002401457700002201481700002201503700002301525700002401548700002401572856011501596 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. uhttp://library.ncl.res.in/content/effects-cis-and-trans-butenedioic-acid-physicochemical-behavior-lumefantrine