01732nas a2200181   4500008004100000245007800041210006900119260000800188300002200196490000700218520109300225100002801318700002001346700002701366700002601393700002001419856011101439       2018                        eng d00aCurcumin-artemisinin coamorphous solid: Xenograft model preclinical study0 aCurcuminartemisinin coamorphous solid Xenograft model preclinica  cMAR  aArticle Number: 70 v103 aCurcumin is a natural compound present in Indian spice turmeric. It has diverse pharmacological action but low oral solubility and bioavailability continue to limit its use as a drug. With the aim of improving the bioavailability of Curcumin (CUR), we evaluated Curcumin-Pyrogallol (CUR-PYR) cocrystal and Curcumin-Artemisinin (CUR-ART) coamorphous solid. Both of these solid forms exhibited superior dissolution and pharmacokinetic behavior compared to pure CUR, which is practically insoluble in water. CUR-ART coamorphous solid showed two fold higher bioavailability than CUR-PYR cocrystal (at 200 mg/kg oral dose). Moreover, in simulated gastric and intestinal fluids (SGF and SIF), CUR-ART is stable up to 3 and 12 h, respectively. In addition, CUR-PYR and CUR-ART showed no adverse effects in toxicology studies (10 times higher dose at 2000 mg/kg). CUR-ART showed higher therapeutic effect and inhibited approximately 62% of tumor growth at 100 mg/kg oral dosage of CUR in xenograft models, which is equal to the positive control drug, doxorubicin (2 mg/kg) by i.v. administration.1 aMannava, M., K. Chaitan1 aSuresh, Kuthuru1 aBommaka, Manish, Kumar1 aKonga, Durga, Bhavani1 aNangia, Ashwini  uhttp://library.ncl.res.in/content/curcumin-artemisinin-coamorphous-solid-xenograft-model-preclinical-study02664nas a2200193   4500008004100000022001400041245011200055210006900167260000800236300001400244490000700258520196300265100002702228700002802255700002002283700002202303700002002325856012502345       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  uhttp://library.ncl.res.in/content/entacapone-improving-aqueous-solubility-diffusion-permeability-and-cocrystal-stability01930nas a2200193   4500008004100000022001400041245008800055210006900143260000900212300001400221490000700235520125800242100002701500700002801527700001901555700002001574700002401594856011801618       2021                        eng d  a1528-748300aEntacapone polymorphs: crystal structures, dissolution, permeability, and stability0 aEntacapone polymorphs crystal structures dissolution permeabilit  cOCT   a5573-55850 v213 aEntacapone (ETP) is a catechol-O-methyltransferase (COMT) drug used to treat Parkinson's disease. ETP is available in the marketplace under the brand name Comtan since 2010, and ETP form-I was first reported in a patent published in 2001. However, analysis of its Xray crystal structures and stability relationship of ETP polymorphs and their dissolution and permeability profile have not yet been reported. We crystallized two new conformational polymorphs of ETP from a water and acetone mixture and studied the structural origin of polymorphism and their phase transformations, stability, equilibrium solubility, dissolution, and permeability properties. The ETP molecule adopts different conformations in the polymorphic structures with slight changes in carbonyl and nitrile group orientations. Thermal analysis suggests that form-III and form-IV are enantiotropically related to form-I, which is the thermodynamically stable form at ambient conditions. In contrast, form-II is monotropically related to form-I. Equilibrium solubility, dissolution, and permeability studies show that form-II persists in the slurry medium and dissolves faster with a high flux rate compared to the stable form-I in phosphate buffer solution at 37 +/- 0.5 degrees C.1 aBommaka, Manish, Kumar1 aMannava, M., K. Chaitan1 aRai, Sunil, K.1 aSuresh, Kuthuru1 aNangia, Ashwini, K.  uhttp://library.ncl.res.in/content/entacapone-polymorphs-crystal-structures-dissolution-permeability-and-stability