00563nas a2200181 4500008004100000022001400041245005800055210005700113260000800170300000900178490000700187653001800194653002000212653001600232100002100248700002000269856009200289 2014 eng d a2053-273300aCrystal engineering principles: fluoroquinolone salts0 aCrystal engineering principles fluoroquinolone salts cAPR aC4130 v7010aciprofloxacin10aFluoroquinolone10anorfloxacin1 aDandela, Rambabu1 aNangia, Ashwini uhttps://library.ncl.res.in/content/crystal-engineering-principles-fluoroquinolone-salts00513nas a2200169 4500008004100000022001400041245004900055210004900104260000800153300000800161490000700169653001500176653002400191653002700215100002000242856008100262 2014 eng d a2053-273300aPharmaceutical solids in crystal engineering0 aPharmaceutical solids in crystal engineering cMAY aC120 v7010acocrystals10acrystal engineering10aSupramolecular synthon1 aNangia, Ashwini uhttps://library.ncl.res.in/content/pharmaceutical-solids-crystal-engineering00686nas a2200181 4500008004100000022001400041245006200055210006200117260000800179300000900187490000700196653012600203100002400329700001800353700001900371700002000390856009400410 2014 eng d a2053-273300aSupramolecular synthon hierarchy in bumetanide cocrystals0 aSupramolecular synthon hierarchy in bumetanide cocrystals cFEB aC7210 v7010aNovel cocrystals of sulfonamide drug Bumetanide with carboxamides are developed based on supramolecular synthons approach1 aAllu, Suryanarayana1 aBolla, Geetha1 aTothadi, Srinu1 aNangia, Ashwini uhttps://library.ncl.res.in/content/supramolecular-synthon-hierarchy-bumetanide-cocrystals01190nas a2200169 4500008004100000245010300041210006900144260000800213300001600221490000700237520057100244100002200815700002000837700002000857700002000877856012300897 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 uhttps://library.ncl.res.in/content/crystal-engineering-zwitterionic-drug-neutral-cocrystals-general-solution-floxacins02338nas a2200157 4500008004100000022001400041245004800055210004700103260011000150300001400260490000700274520178300281100001802064700002002082856007802102 2016 eng d a1359-734500aPharmaceutical cocrystals: walking the talk0 aPharmaceutical cocrystals walking the talk aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcMAY a8342-83600 v523 a

Pharmaceutical cocrystals belong to a sub-class of cocrystals wherein one of the components is a drug molecule (or an active pharmaceutical ingredient, API) and the second is a benign food or drug grade additive (generally regarded as safe, GRAS). The two components are hydrogen-bonded in a fixed stoichiometric ratio in the crystal lattice. In the past decade, pharmaceutical cocrystals have demonstrated significant promise in their ability to modify the physicochemical and pharmacokinetic properties of drug substances, such as the solubility and dissolution rate, bioavailability, particle morphology and size, tableting and compaction, melting point, physical form, biochemical and hydration stability, and permeability. In this feature review, we highlight some prominent examples of drug cocrystals which exhibit variable hardness/softness and elasticity/plasticity depending on coformer selection, improvement of solubility and permeability in the same cocrystal, increase of the melting point for solid formulation, enhanced color performance, photostability and hydration stability, and a longer half-life. Cocrystals of flavanoids and polyphenols can make improved pharmaceuticals and also extend to the larger class of nutraceuticals. The application of crystal engineering to assemble ternary cocrystals expands this field to drug-drug cocrystals which may be useful in multi-drug resistance, mitigating side effects of drugs, or attenuating/enhancing drug action synergistically by rational selection. The advent of new techniques for structural characterization beyond the standard X-ray diffraction will provide a better understanding of drug phases which are at the borderline of crystalline-amorphous nature and even newer opportunities in the future.

1 aBolla, Geetha1 aNangia, Ashwini uhttps://library.ncl.res.in/content/pharmaceutical-cocrystals-walking-talk02176nas a2200205 4500008004100000022001400041245006500055210006300120260007100183300001400254490000700268520145700275100002601732700002301758700002501781700002001806700002101826700002401847856009901871 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. uhttps://library.ncl.res.in/content/syringic-acid-structural-elucidation-and-co-crystallization01962nas a2200193 4500008004100000245014800041210006900189260000800258300001400266490000700280520122900287100001901516700002301535700001701558700002701575700002001602700002001622856012601642 2016 eng d00aTracing the architecture of caffeic acid phenethyl ester cocrystals: studies on crystal structure, solubility, and bioavailability implications0 aTracing the architecture of caffeic acid phenethyl ester cocryst cOCT a5710-57160 v163 a

Caffeic acid phenethyl ester (CAPE) is a polyphenolic active compound present in popular apiproduct, "propolis", obtained from beehives, Though it has broad therapeutic capability, the bioavailability of CAPE is limited due to poor solubility. In this study, we report novel cocrystals of CAPE engineered using coformers such as caffeine (CAP), isonicotinamide (INIC), and nicotinamide (NIC) with enhanced solubility and bioavailability of CAPE. The cocrystals were prepared by microwave-assisted cocrystallization and characterized using PXRD, DSC, and Raman spectroscopy. PXRD and DSC confirm the successful formation and phase purity of CAPE-CAF, CAPE-INIC, and CAPE-NIC cocrystals. Raman spectra of CAPE cocrystals complement these results in confirming the formation of novel crystalline phases. CAPE-NIC cocrystal was further subjected X-ray crystallography to understand its molecular arrangement and hydrogen bonding in the crystal structure. The CAPE-NIC cocrystal structure is found to be stabilized by a rare 1,2-benzenediol-amide heterosynthon. Cocrystallization of CAPE with NIC improved its aqueous solubility and pharmacokinetic profile, thereby demonstrating a 2.76-fold escalation in bioavailability.

1 aKetkar, Sameer1 aPagire, Sudhir, K.1 aGoud, Rajesh1 aMahadik, Kakasaheb, R.1 aNangia, Ashwini1 aParadkar, Anant uhttps://library.ncl.res.in/content/tracing-architecture-caffeic-acid-phenethyl-ester-cocrystals-studies-crystal-structure00573nas a2200133 4500008004100000245012700041210006900168260000800237300001400245490000700259100002500266700002000291856012800311 2016 eng d00aUse of the term "crystal engineering" in the regulatory and patent literature of pharmaceutical solid forms. some comments0 aUse of the term crystal engineering in the regulatory and patent cAUG a5585-55870 v161 aDesiraju, Gautam, R.1 aNangia, Ashwini uhttps://library.ncl.res.in/content/use-term-crystal-engineering-regulatory-and-patent-literature-pharmaceutical-solid-forms02150nas a2200157 4500008004100000245006500041210006300106260000800169300001200177490000600189520163800195100001801833700002501851700002001876856009601896 2017 eng d00a Acemetacin cocrystal structures by powder X-ray diffraction0 aAcemetacin cocrystal structures by powder Xray diffraction cMAY a206-2140 v43 aCocrystals of acemetacin drug (ACM) with nicotinamide (NAM), p-aminobenzoic acid (PABA), valerolactam (VLM) and 2-pyridone (2HP) were prepared by melt crystallization and their X-ray crystal structures determined by high-resolution powder X-ray diffraction. The powerful technique of structure determination from powder data (SDPD) provided details of molecular packing and hydrogen bonding in pharmaceutical cocrystals of acemetacin. ACM-NAM occurs in anhydrate and hydrate forms, whereas the other structures crystallized in a single crystalline form. The carboxylic acid group of ACM forms theacid-amide dimer three-point synthon R-3(2)(9) R-2(2)(8) R-3(2)(9) with three different syn amides (VLM, 2HP and caprolactam). The conformations of the ACM molecule observed in the crystal structures differ mainly in the mutual orientation of chlorobenzene fragment and the neighboring methyl group, being anti (type I) or syn (type II). ACM hydrate, ACM-NAM, ACM-NAM-hydrate and the piperazine salt of ACM exhibit the type I conformation, whereas ACM polymorphs and other cocrystals adopt the ACM type II conformation. Hydrogen-bond interactions in all the crystal structures were quantified by calculating their molecular electrostatic potential (MEP) surfaces. Hirshfeld surface analysis of the cocrystal surfaces shows that about 50% of the contribution is due to a combination of strong and weak O center dot center dot center dot H, N center dot center dot center dot H, Cl center dot center dot center dot H and C center dot center dot center dot H interactions. The physicochemical properties of these cocrystals are under study.1 aBolla, Geetha1 aChernyshev, Vladimir1 aNangia, Ashwini uhttps://library.ncl.res.in/content/acemetacin-cocrystal-structures-powder-x-ray-diffraction01819nas a2200265 4500008004100000022001400041245010100055210006900156260000800225300001200233490000600245520092600251653001901177653002401196653002001220653002101240653003201261653002201293653002101315653001701336100002301353700002801376700002001404856012901424 2017 eng d a2052-252500aMechanochemical synthesis of N-salicylideneaniline: thermosalient effect of polymorphic crystals0 aMechanochemical synthesis of Nsalicylideneaniline thermosalient  cMAY a243-2500 v43 a

Polymorphs of the dichloro derivative of N-salicylideneaniline exhibit mechanical responses such as jumping (Forms I and III) and exploding (Form II) in its three polymorphs. The molecules are connected via the amide N-H center dot center dot center dot O dimer synthon and C-Cl center dot center dot center dot O halogen bond in the three crystal structures. A fourth high-temperature Form IV was confirmed by variable-temperature single-crystal X-ray diffraction at 180 degrees C. The behaviour of jumping exhibited by the polymorphic crystals of Forms I and III is due to the layered sheet morphology and the transmission of thermal stress in a single direction, compared with the corrugated sheet structure of Form II such that heat dissipation is more isotropic causing blasting. The role of weak C-Cl center dot center dot center dot O interactions in the thermal response of molecular crystals is discussed.

10acrystal design10acrystal engineering10aHalogen bonding10ahydrogen bonding10aintermolecular interactions10amaterials science10amechanochemistry10apolymorphism1 aMittapalli, Sudhir1 aPerumalla, Sravanakumar1 aNangia, Ashwini uhttps://library.ncl.res.in/content/mechanochemical-synthesis-n-salicylideneaniline-thermosalient-effect-polymorphic-crystals01885nas a2200181 4500008004100000022001400041245008900055210006900144260000900213300001200222490000700234520125200241100002001493700002801513700002201541700002001563856012001583 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 uhttps://library.ncl.res.in/content/polymorphism-isostructurality-and-physicochemical-properties-glibenclamide-salts01861nas a2200169 4500008004100000245007400041210006900115260000800184300001400192490000700206520129100213100002401504700001801528700001901546700002001565856010601585 2017 eng d00aSupramolecular synthons in bumetanide cocrystals and ternary products0 aSupramolecular synthons in bumetanide cocrystals and ternary pro cAUG a4225-42360 v173 aA novel design strategy for cocrystals of the diuretic sulfonamide drug bumetanide (BUM) with carboxamides is reported based on reliable supramolecular synthons. Binary cocrystals of BUM with pyridine carboxamides, pyridones, and cytosine were obtained by solvent assisted grinding followed by solution crystallization. All cocrystal structures exhibit hydrogen bonding of the coformer with the carboxylic acid group of BUM via heterosynthons which replace the acid homodimer in the drug crystal structure. Pyridones are inserted as N-H center dot center dot center dot O dimers which are in turn bonded to the acid group of BUM, while the pyridine amide coformers interact via the acid amide heterosynthon. Cocrystal polymorphs were obtained for bumetanide isonicotinamide cocrystal structure with the sulfonamide pyridine and sulfonamide acid synthons. Careful crystal packing analysis of BUM structure and nine new binary adducts gave an idea for the design ternary cocrystals, and subsequently four new ternary crystalline products were crystallized. Whereas the binary cocrystal structures were confirmed by single crystal diffraction, the ternary combinations were chatacterized by their unique powder X-ray diffraction patterns as well as by thermal and spectroscopic techniques.1 aAllu, Suryanarayana1 aBolla, Geetha1 aTothadi, Srinu1 aNangia, Ashwini uhttps://library.ncl.res.in/content/supramolecular-synthons-bumetanide-cocrystals-and-ternary-products02488nas a2200169 4500008004100000245009200041210006900133260000800202300001200210490000600222520187300228100002302101700002802124700003002152700002002182856011602202 2017 eng d00aThermomechanical effect in molecular crystals: the role of halogen-bonding interactions0 aThermomechanical effect in molecular crystals the role of haloge cNOV a812-8230 v43 aThe design and synthesis of mechanically responsive materials is interesting because they are potential candidates to convert thermal energy into mechanical work. Reported in this paper are thermosalient effects in a series of halogen derivatives of salinazids. The chloro derivative, with higher electronegativity and a weaker inter-halogen bond strength (Cl center dot center dot center dot Cl) exhibits an excellent thermal response, whereas the response is weaker in the iodo derivative with stronger I center dot center dot center dot I halogen bonding. 3,5-Dichlorosalinazid (Compound-A) exists in three polymorphic forms, two room-temperature polymorphs (Forms I and II) and one high-temperature modification (Form III). The transformation of Form I to Form III upon heating at 328-333 K is a reversible thermosalient transition, whereas the transformation of Form II to Form III is irreversible and nonthermosalient. 3,5-Dibromo- (Compound-B) and 3-bromo-5-chloro(Compound-C) salinazid are both dimorphic: the Form I to Form II transition in Compound-B is irreversible, whereas Compound-C shows a reversible thermosalient effect (362-365 K). In the case of 3,5-diiodosalinazid (CompoundD) and 3,5-difluorosalinazid (Compound-E), no phase transitions or thermal effects were observed. The thermosalient behaviour of these halosalinazid molecular crystals is understood from the anisotropy in the cell parameters (an increase in the a axis and a decrease in the b and c axes upon heating) and the sudden release of accumulated strain during the phase transition. The dihalogen salinazid derivatives (chlorine to iodine) show a decrease in thermal effects with an increase in halogen-bond strength. Interestingly, Compound-B shows solid-state photochromism in its polymorphs along with the thermosalient effect, wherein Form I is cyan and Form II is light orange.1 aMittapalli, Sudhir1 aPerumalla, Sravanakumar1 aNanubolu, Jagadeesh, Babu1 aNangia, Ashwini uhttps://library.ncl.res.in/content/thermomechanical-effect-molecular-crystals-role-halogen-bonding-interactions01918nas a2200145 4500008004100000245009200041210006900133260000800202300001400210490000700224520138300231100002001614700002001634856011801654 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 uhttps://library.ncl.res.in/content/curcumin-pharmaceutical-solids-platform-improve-solubility-and-bioavailability01733nas a2200181 4500008004100000245007800041210006900119260000800188300002200196490000700218520109300225100002801318700002001346700002701366700002601393700002001419856011201439 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 uhttps://library.ncl.res.in/content/curcumin-artemisinin-coamorphous-solid-xenograft-model-preclinical-study02665nas 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-stability01736nas a2200145 4500008004100000245004700041210004600088260000800134300001500142490000700157520131000164100001801474700002001492856007801512 2018 eng d00a Novel pharmaceutical salts of albendazole0 aNovel pharmaceutical salts of albendazole cNOV a 6394-64050 v203 aAlbendazole (ABZ) is a class II safe and effective antihelmintic drug in the benzimidazole group according to the BCS (Biopharmaceutics Classification System) with low solubility (9 mg L-1) and high permeability (log P 2.54). Novel salts and salt hydrates of ABZ are reported with benzene and p-toluene sulfonic acid (BSA, PTSA), as well as carboxylic acids such as oxalic acid (OA), maleic acid (MLE), L-tartaric acid (LTA), 2,6-dihydroxybenzoic acid (2,6-DHBA), and 2,4,6-trihydroxybenzoic acid (2,4,6-THBA). The products ABZ-BSA, ABZ-BSA-H, ABZ-PTSA, ABZ-PTSA-H, ABZ-OA-H and ABZ-2,6-DHBA were confirmed by single crystal X-ray diffraction. In the hydrate structures (designated as -H), the water molecule acts as a bridge in the hydrogen bonding network. The salt formation of ABZ-MLE, ABZ-LTA, and ABZ-2,4,6-THBA was confirmed by N-15 ss-NMR based on the chemical shift change of ca. 50 ppm. The sulfonate salt hydrates exhibit 2D isostructurality, and position disorder in the thiopropyl group in the drug crystal structure was not observed in the salts. Crystal lattice energies were calculated for the MLE, LTA, and 2,4,6-THBA complexes of ABZ to confirm the molecular salt formation. The cocrystals of ABZ with the hydroxybenzene carboxylic acids are novel salts in the benzimidazole drugs class.1 aBolla, Geetha1 aNangia, Ashwini uhttps://library.ncl.res.in/content/novel-pharmaceutical-salts-albendazole03011nas 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-characterization02160nas a2200157 4500008004100000245006700041210006700108260000800175300001400183490000700197520164100204100002201845700002001867700002001887856009501907 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 uhttps://library.ncl.res.in/content/salts-and-salt-cocrystals-antibacterial-drug-pefloxacin02362nas a2200181 4500008004100000022001500041245013900056210006900195260000800264300001200272490000600284520167300290100002101963700001901984700002602003700002002029856013102049 2018 eng d a 2052-252500a Systematic synthesis of a 6-component organic-salt alloy of naftopidil, and pentanary, quaternary and ternary multicomponent crystals0 aSystematic synthesis of a 6component organicsalt alloy of naftop cNOV a816-8220 v53 aThe single-crystal X-ray structure of a 6-component organic-salt alloy (hexanary) of naftopidil (1) (an active pharmaceutical ingredient) with benzoic acid (2) and four different hydroxy-substituted benzoic acids, i.e. salicylic acid (3), 2,3-dihydroxybenzoic acid (4), 2,4-dihydroxybenzoic acid (5) and 2,6-dihydroxybenzoic acid (6), is reported. The hexanary assembly originates from the observation that the binary salts of naftopidil with the above acids are isostructural. In addition to the 6-component solid, we also describe five 5-component, ten 4-component, and ten 3-component organic-salt alloys of naftopidil (1) with carboxylic acids (2)-(6). These alloys were obtained from different combinations of the acids with the drug. The synthetic design of the multicomponent organic alloys is based on the rationale of geometrical factors (shape and size) and chemical interactions (hydrogen bonds). The common supramolecular synthon in all these crystal structures was the cyclic N+ - H center dot center dot center dot O- and O-H center dot center dot center dot O hydrogen-bonded motif of R-2(2) (9) graph set between the 2-hydroxyammonium group of naftopidil and the carboxylate anion. This ionic synthon is strong and robust, directing the isostructural assembly of naftopidil with up to five different carboxylic acids in the crystal structure together with the lower-level multicomponent adducts. Solution crystallization by slow evaporation provided the multicomponent organic salts and alloys which were characterized by a combination of single-crystal X-ray diffraction, powder X-ray diffraction, NMR and differential scanning calorimetry techniques.1 aDandela, Rambabu1 aTothadi, Srinu1 aMarelli, Udaya, Kiran1 aNangia, Ashwini uhttps://library.ncl.res.in/content/systematic-synthesis-6-component-organic-salt-alloy-naftopidil-and-pentanary-quaternary-and02581nas a2200181 4500008004100000022001400041245010000055210006900155260000800224300001200232490000700244520192800251100002302179700002802202700001902230700002002249856013002269 2019 eng d a1528-748300aCocrystals, salts, and supramolecular gels of nonsteroidal anti inflammatory drug niflumic acid0 aCocrystals salts and supramolecular gels of nonsteroidal anti in cJAN a219-2300 v193 a

Niflumic acid (NFA) is a nonsteroidal anti-inflammatory drug (NSAID) classified under the BCS (Biopharmaceutical Classification System) Class II category of poor aqueous solubility and high permeability. In an attempt to improve the physicochemical properties of NFA, particularly solubility and dissolution rate by cocrystallization and salt formation, cocrystals of NFA were prepared with caprolactam (CPR, 1:1) and 2-hydroxy pyridine (2HP, 1:1) as well as salts with piperazine (PIP, 1:0.5), benzenesulfonic acid (BSA, 1:1), benzyl amine (BZA, 1:1 and 2:2), and tyramine (TYA, 1:1). The new solid forms were characterized by powder X-ray diffraction, infrared spectroscopy, and differential scanning calorimetry and confirmed by single crystal X-ray diffraction. In the cocrystals NFA CPR and NFA-2HP, the cyclic amide of the coformer forms a dimer synthon through N-H center dot center dot center dot O hydrogen bonds and such dimers extend through O-H center dot center dot center dot O hydrogen bonds. In piperazine, benzyl amine, and tyramine salts, proton transfer occurs from the NFA to the basic nitrogen of the coformer, and in NFA BSA salt, the proton is transferred from benzenesulfonic acid to the pyridine nitrogen of NFA. In addition to the above salts and cocrystals, supramolecular gels of NFA-PIP and NFA-BZA salts are reported, which were obtained from nitrobenzene, methyl salicylate, menthol, and mesitylene solvents. These gels were studied by rheology. Solubility and dissolution rate of the novel solid forms (NFA CPR, NFA PIP, NFA BSA, and NFA TYA) in 20% EtOH water showed the best behavior for NFA-TYA salt with improvement of 42-and 54-times in solubility and dissolution rate compared to the reference drug. The remaining solids such as NFA-PIP, NFA-BSA salts, and NFA-CPR cocrystal exhibited improvement of 39-, 18-, 1.4-times in solubility and 7.8-, 10-, 2-times for dissolution rate.

1 aMittapalli, Sudhir1 aMannava, M., K. Chaitan1 aSahoo, Rasmita1 aNangia, Ashwini uhttps://library.ncl.res.in/content/cocrystals-salts-and-supramolecular-gels-nonsteroidal-anti-inflammatory-drug-niflumic-acid01944nas a2200241 4500008004100000022001400041245007900055210006900134260000800203300001400211490000700225520118000232100001801412700001701430700002401447700002201471700002101493700002201514700002001536700001801556700001901574856010901593 2019 eng d a1528-748300aCrystalline acylhydrazone photoswitches with multiple mechanical responses0 aCrystalline acylhydrazone photoswitches with multiple mechanical cMAY a3039-30440 v193 a

The advancement of our understanding of stimuli responsive molecular crystals has led to the realization that they hold great yet unexplored potential as adaptive materials. Although molecular crystals that exhibit a single mechanical response to a single input stimulus are now abundant, crystals that are capable of response to multiple stimuli are rather scarce. Here we report two photoswitchable acylhydrazone derivatives, Ac-1 and Ac-2, which respond to light as well as to mechanical force. Upon application of localized mechanical stress, the anhydrous (Ac-1a) and monohydrate (Ac-1h) crystals of Ac-1 undergo plastic shearing deformation and bending, whereas monohydrate crystals of Ac-2 undergo elastic deformation. When they are exposed to UV light, crystals of Ac-1h and Ac-2 undergo photoinduced bending; on the other hand, crystals of Ac-1a and thicker crystals of Ac-2 exhibit photosalient effect (light-induced leaping). It is demonstrated that the synergistic action of multiple stimuli (UV light and force) elicits enhanced mechanical response, and this strategy could be employed in the future to increase the efficacy of single crystal actuators.

1 aGupta, Poonam1 aPanda, Tamas1 aAllu, Suryanarayana1 aBorah, Silpisikha1 aBaishya, Anamika1 aGunnam, Anilkumar1 aNangia, Ashwini1 aNaumov, Pance1 aNath, Naba, K. uhttps://library.ncl.res.in/content/crystalline-acylhydrazone-photoswitches-multiple-mechanical-responses00402nas a2200145 4500008004100000245002900041210002900070260000800099300001200107490000600119100002500125700002200150700002000172856006400192 2019 eng d00aElectron crystallography0 aElectron crystallography cSEP a786-7870 v61 aBlake, Alexander, J.1 ade Boissieu, Marc1 aNangia, Ashwini uhttps://library.ncl.res.in/content/electron-crystallography02636nas a2200265 4500008004100000022001400041245012500055210006900180260000900249300001200258490000800270520175800278653001702036653001602053653000802069653000802077653002702085653001702112100002102129700002202150700002802172700002002200700002402220856012602244 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. uhttps://library.ncl.res.in/content/quantification-niclosamide-polymorphic-forms-comparative-study-raman-nir-and-mir-using01119nas a2200193 4500008004100000022001400041245009400055210006900149260000900218300001400227490000700241520045000248100002400698700002000722700001800742700002800760700002000788856011700808 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 uhttps://library.ncl.res.in/content/role-hydrogen-bonding-cocrystals-and-coamorphous-solids-indapamide-case-study01899nas a2200217 4500008004100000022001400041245009200055210006900147260000800216300001200224490000600236520118300242653001501425653002401440653001701464653002801481653001501509100001801524700002001542856011901562 2019 eng d a2052-252500aSupramolecular synthon hierarchy in sulfonamide cocrystals with syn-amides and N-oxides0 aSupramolecular synthon hierarchy in sulfonamide cocrystals with  cJUL a751-7600 v63 a

Sulfonamide drugs are well known antibacterial and antimicrobial molecules for pharmaceutical development. Building a library of suitable supramolecular synthons for the sulfonamide functional group and understanding their crystal structures with partner coformer molecules continues to be a challenge in crystal engineering. Although a few sulfonamide cocrystals with amides and N-oxides have been reported, the body of work on sulfonamide synthons is limited compared with those that have carboxylic acids and carboxamides. To address this structural gap, the present work is primarily focused on sulfonamide-lactam and sulfonamide-syn-amide synthons with drugs such as celecoxib, hydrochlorothiazide and furosemide. Furthermore, the electrostatic potential of previously reported cocrystals has been recalculated to show that the negative electrostatic potential on the lactam and syn-amide O atom is higher compared with the charge on carboxamide and pyridine N-oxide O atoms. The potential of sulfonamide molecules to form cocrystals with syn-amides and lactams are evaluated in terms of the electrostatic potential energy for the designed supramolecular synthons.

10acocrystals10acrystal engineering10asulfonamides10asupramolecular synthons10asyn-amides1 aBolla, Geetha1 aNangia, Ashwini uhttps://library.ncl.res.in/content/supramolecular-synthon-hierarchy-sulfonamide-cocrystals-syn-amides-and-n-oxides01087nas a2200193 4500008004100000245008900041210006900130260000800199300001400207490000700221520042400228100002600652700002200678700002100700700001900721700002000740700002100760856011200781 2021 eng d00aSeparation of a diastereomeric diol pair using the mechanical properties of crystals0 aSeparation of a diastereomeric diol pair using the mechanical pr cOCT a7056-70600 v233 aWe report the separation of a (2S,3R/S)-3-ethyl-1-phenylhex-5-ene-2,3-diol (ephd) diastereomeric pair with visually indistinguishable acicular morphologies based on their mechanical responses, which is found to be more efficient than conventional separation methods. Furthermore, the molecular crystals of (2S,3R)-ephd show elastic deformation, while (2S,3S)-ephd fractures in a brittle manner under similar conditions.1 aGamidi, Rama, Krishna1 aDandawate, Monica1 aChoudhury, Rahul1 aTothadi, Srinu1 aNangia, Ashwini1 aReddy, Srinivasa uhttps://library.ncl.res.in/content/separation-diastereomeric-diol-pair-using-mechanical-properties-crystals01907nas a2200205 4500008004100000022001400041245010500055210006900160260000800229300001400237490000800251520118200259100002601441700001901467700002501486700002901511700002001540700002301560856011801583 2025 eng d a1932-744700aResolving salt-cocrystal conundrum in multicomponent crystals by using X-ray quantum crystallography0 aResolving saltcocrystal conundrum in multicomponent crystals by  cMAY a9169-91780 v1293 a

The structural identity of multicomponent crystals as a salt or cocrystal is dictated by the proton transfer state between the molecular components. In pharmaceutical drugs, solid-state forms such as salts or cocrystals can have significantly distinct stability, dissolution, and solubility profiles. The accurate location of proton positions is a formidable task using conventional X-ray crystallography, as the atomic scattering factors are based on spherical electron density models. Herein, we demonstrate that the X-ray quantum crystallographic (QCr) technique of Hirshfeld Atom Refinement (HAR), based on aspherical atomic scattering factors, can be effectively employed to resolve this riddle. Our HAR models accurately located the proton positions, thus distinguishing salts, cocrystals, and continuum crystal structures, which are substantiated by the N 1s binding energies from X-ray photoelectron spectroscopy (XPS) corresponding to the base components in a series of crystals. The QCr models reveal the subtle features of electron localization and bonding around the double-well potential in the intermolecular proton-transfer regions in these crystals.

1 aSudheendranath, Athul1 aTothadi, Srinu1 aPradhan, Amit, Kumar1 aPrajapati, Aditya, Kumar1 aNangia, Ashwini1 aThomas, Sajesh, P. uhttps://library.ncl.res.in/content/resolving-salt-cocrystal-conundrum-multicomponent-crystals-using-x-ray-quantum