02665nas a2200193   4500008004100000022001400041245011200055210006900167260000800236300001400244490000700258520196300265100002702228700002802255700002002283700002202303700002002325856012602345       2018                        eng d  a1528-748300aEntacapone: improving aqueous solubility, diffusion permeability, and cocrystal stability with theophylline0 aEntacapone improving aqueous solubility diffusion permeability a  cOCT  a6061-60690 v183 aCocrystallization is a well-established technique to improve the solubility, bioavailability, and stability of active pharmaceutical ingredients (APIs) but permeability and diffusion rate control via cocrystals is relatively less well studied, and the exact role of coformers in influencing the diffusion rate of drug cocrystals is still not fully understood. The aqueous solubility and permeability diffusion of Entacapone, ETP, a Biopharmaceutical Classification System (BCS) Class IV drug of low solubility and low permeability, with Generally Regarded as Safe (GRAS) coformers has been studied. Fixed stoichiometry cocrystals of ETP with acetamide (ACT, 1:1), nicotinamide (NAM, 1:1), isonicotinamide (INAM, 1:1), pyrazinamide (PYZ, 1:1), and isoniazid (INZ), 1:1) were prepared by solvent-assisted grinding. Theophylline (THP) resulted in a cocrystal hydrate (ETP-THP-FIYD 1:1:1). The cocrystals were structurally characterized by single crystal and powder X-ray diffraction, DSC and TGA thermal measurements, and IR and NMR spectroscopy. Solubility and dissolution rate showed that there is a correlation between cocrystal stability and solubility governed by the heteromeric N-H center dot center dot center dot O, O-H center dot center dot center dot N, and O-H center dot center dot center dot O hydrogen bonds and conformational changes of ETP in cocrystal structures. ETP-THP-HYD and ETP-PYZ exhibit faster dissolution rate and high solubility and they are stable in phosphate buffer medium compared to the other cocrystals which dissociate partially during solubility experiments. Diffusion rates in a Franz cell showed that the stable and high solubility ETP-THP-HYD cocrystal has good permeability. Given that stability, solubility, and permeability are in general inversely correlated, the entacapone-theophylline hydrate cocrystal is a unique example of the thermodynamically stable cocrystal exhibiting high solubility and high permeability.1 aBommaka, Manish, Kumar1 aMannava, M., K. Chaitan1 aSuresh, Kuthuru1 aGunnam, Anilkumar1 aNangia, Ashwini  uhttps://library.ncl.res.in/content/entacapone-improving-aqueous-solubility-diffusion-permeability-and-cocrystal-stability02110nas 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<p>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.</p>
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