03011nas a2200277 4500008004100000022001400041245007900055210006900134260000800203300001200211490000800223520215300231653002002384653002202404653000802426653001602434653001502450100001802465700002602483700002202509700002202531700002302553700002002576700002402596856011302620 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. uhttps://library.ncl.res.in/content/rufinamide-crystal-structure-elucidation-and-solid-state-characterization02161nas a2200193 4500008004100000245010900041210006900150260000800219490000800227520145000235100002201685700002201707700002801729700001901757700001901776700002401795700002401819856012401843 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. uhttps://library.ncl.res.in/content/co-amorphous-valsartan-nifedipine-system-preparation-characterization-vitro-and-vivo02110nas a2200205 4500008004100000022001400041245010300055210006900158260000900227300001200236490000700248520138000255100002801635700002201663700002201685700002401707700002401731700001901755856013001774 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 uhttps://library.ncl.res.in/content/enhanced-solubility-permeability-and-tabletability-nicorandil-salt-and-cocrystal-formation01942nas 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-lumefantrine