01189nas a2200169 4500008004100000245010300041210006900144260000800213300001600221490000700237520057100244100002200815700002000837700002000857700002000877856012200897 2016 eng d00aCrystal engineering of a zwitterionic drug to neutral cocrystals: a general solution for floxacins0 aCrystal engineering of a zwitterionic drug to neutral cocrystals cSEP a12610-126130 v523 a

The transformation of zwitterionic Sparfloxacin (SPX) to the neutral form is achieved by cocrystallization. Neutral forms of drugs are important for higher membrane permeability, while zwitterions are more soluble in water. The twin advantages of higher solubility/dissolution rate and good stability of neutral SPX are achieved in a molecular cocrystal compared to its zwitterionic SPX hydrate. The amine-phenol supra-molecular synthon drives cocrystal formation, with the paraben ester acting as a "proton migrator'' for the ionic to neutral transformation.

1 aGunnam, Anilkumar1 aSuresh, Kuthuru1 aGanduri, Ramesh1 aNangia, Ashwini uhttp://library.ncl.res.in/content/crystal-engineering-zwitterionic-drug-neutral-cocrystals-general-solution-floxacins01884nas a2200181 4500008004100000022001400041245008900055210006900144260000900213300001200222490000700234520125200241100002001493700002801513700002201541700002001563856011901583 2017 eng d a1466-803300aPolymorphism, isostructurality and physicochemical properties of glibenclamide salts0 aPolymorphism isostructurality and physicochemical properties of  cFEB  a918-9290 v193 a

Novel salts of glibenclamide (GBA), namely glibenclamide-sodium (GBA-Na), glibenclamide-potassium (GBA-K) and glibenclamide-ammonium (GBA-NH4) were crystallized under different conditions to obtain their polymorphs, and their aqueous solubility and hydration stability studies are reported. The GBA-Na salt is dimorphic (forms I and II)and also exists as hydrate GBA-Na-H2O (form III). The GBA-K salt exists in anhydrous and hydrate forms (GBA-K, forms I and II). Crystal structure analysis of GBA-Na forms I and II showed differences in geometry of the central metal atom and ligand orientation. This kind of polymorphism of sulfonyl urea salts appears to be novel in the Cambridge Structural Database (CSD). The iso-structurality of GBA-Na form I with GBA-NH4 and GBA-K form I salts is discussed. The potassium salts of GBA exhibited higher solubility compared to pure GBA. Specifically GBA-K salt forms I and II showed higher solubility by 77 fold in the water and 33 fold in phosphate buffer (pH 7) compared to the other salts. Dynamic vapor sorption (DVS) showed reversible water sorption without hysteresis for all salts, except for GBA-K form II which transformed to form I after a sorption and desorption cycle as confirmed by PXRD.

1 aSuresh, Kuthuru1 aKhandavilli, U., B. Rao1 aGunnam, Anilkumar1 aNangia, Ashwini uhttp://library.ncl.res.in/content/polymorphism-isostructurality-and-physicochemical-properties-glibenclamide-salts01917nas a2200145 4500008004100000245009200041210006900133260000800202300001400210490000700224520138300231100002001614700002001634856011701654 2018 eng d00aCurcumin: pharmaceutical solids as a platform to improve solubility and bioavailability0 aCurcumin pharmaceutical solids as a platform to improve solubili cJUN a3277-32960 v203 aCurcumin (CUR) is the prime curcuminoid in the Indian dietary spice turmeric, Curcuma longa, a plant of the Zingiberaceae family. CUR has promising and diverse therapeutic benefits, such as antioxidant, anti-inflammatory, antitumor, anti-hyperglycemic, antimalarial, antibacterial, and antiviral activity, including anti-Alzheimer's disease. However, CUR is yet to reach the status of a therapeutic drug candidate mainly because a standard solid dosage of curcumin suffers from poor oral bioavailability (0.05 g mL(-1), less than 1%). The reasons behind its low bioavailability include poor solubility (<8 g mL(-1) in water), low permeability and absorption, and rapid metabolism (short elimination half-life of <2 h). A successful CUR therapy requires an appropriate formulation system that will enhance the bioavailability and offer greater therapeutic efficacy. This review covers a comprehensive description of the CUR pharmaceutical solids, such as polymorphs, cocrystals, eutectics, and coamorphous solid-state forms with aim to determine ways to improve its physicochemical properties, including dissolution rate, solubility, physicochemical stability, mechanical strength, compressibility for tablet formation, and oral bioavailability. The cumulative publications in the past decade have forecast a bright future for development of an oral drug formulation of curcumin.1 aSuresh, Kuthuru1 aNangia, Ashwini uhttp://library.ncl.res.in/content/curcumin-pharmaceutical-solids-platform-improve-solubility-and-bioavailability01732nas 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-stability02159nas a2200157 4500008004100000245006700041210006700108260000800175300001400183490000700197520164100204100002201845700002001867700002001887856009401907 2018 eng d00aSalts and salt cocrystals of the antibacterial drug pefloxacin0 aSalts and salt cocrystals of the antibacterial drug pefloxacin cMAY a2824-28350 v183 aPefloxacin (PEF) is an amphoteric, antibacterial drug which exists as a neutral molecule in the crystal structure stabilized by C-H center dot center dot center dot O and C-H center dot center dot center dot F interactions. The design of multicomponent solids using crystal engineering was undertaken in a cocrystal/salt screen of PEF with generally recognized as safe (GRAS) dicarboxylic acids to improve the solubility and phase stability of the drug. Ten multicomponent forms, namely, five salts, two salt hydrates, and three salt cocrystals, were prepared by liquid-assisted grinding followed by crystallization. In some cases, salt and salt cocrystals were obtained concomitantly during solution evaporative crystallization. Single crystal X-ray diffraction showed that the structures are stabilized by N+-H center dot center dot center dot O-, O-H center dot center dot center dot O, C-H center dot center dot center dot O, C-H center dot center dot center dot F, and pi-pi stacking interactions. The bulk phase purity of multicomponent forms was characterized by powder X-ray diffraction, spectroscopy, and thermal techniques. The salt/salt cocrystal forms exhibit a faster dissolution rate and higher solubility compared to pure PEF in pH 1.2 (acidic, like gastric environment) and pH 7 phosphate buffer media (neutral, like intestinal passage). Specifically the PEF+-SA(-) salt (SA = succinic acid) showed remarkably high solubility, dissolution rate, and stability compared to the other multicomponent forms and PEF neutral form. The drug formulation compatible pefloxacin succinate is a promising soluble and stable PEF salt.1 aGunnam, Anilkumar1 aSuresh, Kuthuru1 aNangia, Ashwini uhttp://library.ncl.res.in/content/salts-and-salt-cocrystals-antibacterial-drug-pefloxacin01118nas a2200193 4500008004100000022001400041245009400055210006900149260000900218300001400227490000700241520045000248100002400698700002000722700001800742700002800760700002000788856011600808 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 uhttp://library.ncl.res.in/content/role-hydrogen-bonding-cocrystals-and-coamorphous-solids-indapamide-case-study01930nas 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