Liquid-assisted Grinding Method Research Articles

CHARACTERISATION, EVALUATION AND DENSITY FUNCTIONAL ANALYSIS OF CILNIDIPINE-NICOTINAMIDE COCRYSTALS DEVELOPED BY LIQUID ASSISTED GRINDING TECHNIQUE: A SUSTAINABLE APPROACH FOR ENHANCED SOLUBILITY

Objective: Improving the solubility of poorly water-soluble drugs has always been a challenge in drug development. This study aimed to enhance the aqueous solubility of a poorly water-soluble drug, Cilnidipine, by cocrystallisation method using liquid-assisted grinding (LAG) technique with Nicotinamide as the coformer. The study also aimed to understand the mechanism of cocrystal formation by quantum mechanical calculations. Methods: The Cilnidipine-Nicotinamide cocrystals were prepared in various stoichiometric ratios using the liquid-assisted grinding (LAG) technique. The cocrystals obtained were characterised by vibrational spectroscopy, thermal methods such as differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and surface morphology by field emission scanning electron microscopy (FE-SEM). The cocrystals were evaluated for saturation solubility, and the mechanistic study of cocrystal formation was performed using the Gaussian 09 software package. Results: FT-IR spectra of the formulated cocrystal indicated the intermolecular hydrogen bond formation between-N-H of Nicotinamide and the nitro group of Cilnidipine. DSC analysis showed a single endotherm at 96.76 °C, PXRD patterns were different from that of the reactants, and FE-SEM analysis revealed the changes in the surface morphology of the obtained cocrystal. The prepared cocrystal showed a 26.36-fold enhancement in the aqueous solubility of Cilnidipine. The DFT study demonstrated the formation of a strong intermolecular hydrogen bonding between the nitro-oxygen atom of Cilnidipine and the amide hydrogen atom of Nicotinamide in cocrystal formed. Conclusion: This study highlights the potential of the liquid-assisted grinding method for preparing cocrystals as a sustainable and reliable approach to address the challenges posed by poorly water-soluble drugs.

Enhancing Solubility and Dissolution Rate of Antifungal Drug Ketoconazole through Crystal Engineering.

To improve the solubility and dissolution rate of the BCS class II drug ketoconazole, five novel solid forms in 1:1 stoichiometry were obtained upon liquid-assisted grinding, slurry, and slow evaporation methods in the presence of coformers, namely, glutaric, vanillic, 2,6-dihydroxybenzoic, protocatechuic, and 3,5-dinitrobenzoic acids. Single-crystal X-ray diffraction analysis revealed that the hydroxyl/carboxylic acid. . .N-imidazole motif acts as the dominant supramolecular interaction in the obtained solid forms. The solubility of ketoconazole in distilled water significantly increased from 1.2 to 2165.6, 321.6, 139.1, 386.3, and 191.7 μg mL-1 in the synthesized multi-component forms with glutaric, vanillic, 2,6-dihydroxybenzoic, protocatechuic, and 3,5-dinitrobenzoic acid, respectively. In particular, the cocrystal form with glutaric acid showed an 1800-fold solubility increase in water concerning ketoconazole. Our study provides an alternative approach to improve the solubility and modify the release profile of poorly water-soluble drugs such as ketoconazole.

Accelerated Wound Healing with a Diminutive Scar through Cocrystal Engineered Curcumin.

Pharmaceutical cocrystals ( Regulatory Classification of Pharmaceutical Co-Crystals Guidance for Industry; Food and Drug Administration, 2018) are crystalline solids produced through supramolecular chemistry to modulate the physicochemical properties of active pharmaceutical ingredients (APIs). Despite their extensive development in interdisciplinary sciences, this is a pioneering study on the efficacy of pharmaceutical cocrystals in wound healing and scar reducing. Curcumin-pyrogallol cocrystal (CUR-PYR) was accordingly cherry-picked since its superior physicochemical properties adequately compensate for limitative drawbacks of curcumin (CUR). CUR-PYR has been synthesized by a liquid-assisted grinding (LAG) method and characterized via FT-IR, DSC, and PXRD analyses. In vitro antibacterial study indicated that CUR-PYR cocrystal, CUR+PYR physical mixture (PM), and PYR are more effective against both Gram-negative (Pseudomonas aeruginosa and Escherichia coli) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria in comparison with CUR. In vitro results also demonstrated that the viability of HDF and NIH-3T3 cells treated with CUR-PYR were improved more than those received CUR which is attributed to the effect of PYR in the form of cocrystal. The wound healing process has been monitored through a 15 day in vivo experiment on 75 male rats stratified into six groups: five groups treated by CUR-PYR+Vaseline (CUR-PYR.ung), CUR+PYR+Vaseline (CUR+PYR.ung), CUR+Vaseline (CUR.ung), PYR+Vaseline (PYR.ung), and Vaseline (VAS) ointments and a negative control group of 0.9% sodium chloride solution (NS). It was revealed that the wounds under CUR-PYR.ung treatment closed by day 12 postsurgery, while the wounds in other groups failed to reach the complete closure end point until the end of the experiment. Surprisingly, a diminutive scar (3.89 ± 0.97% of initial wound size) was observed in the CUR-PYR.ung treated wounds by day 15 after injury, followed by corresponding values for PYR.ung (12.08 ± 2.75%), CUR+PYR.ung (13.89 ± 5.02%), CUR.ung (16.24 ± 6.39%), VAS (18.97 ± 6.89%), and NS (20.33 ± 5.77%). Besides, investigating histopathological parameters including inflammation, granulation tissue, re-epithelialization, and collagen deposition signified outstandingly higher ability of CUR-PYR cocrystal in wound healing than either of its two constituents separately or their simple PM. It was concluded that desired solubility of the prepared cocrystal was essentially responsible for accelerating wound closure and promoting tissue regeneration which yielded minimal scarring. This prototype research suggests a promising application of pharmaceutical cocrystals for the purpose of wound healing.

Salts of S-(+)-Ibuprofen Formed via Its Reaction with the Antifibrinolytic Agents Aminocaproic Acid and Tranexamic Acid: Synthesis and Characterization

The paucity of multi-component compounds containing the non-steroidal anti-inflammatory drug (NSAID) S-(+)-ibuprofen (S-IBU) in combination with other drugs prompted the present study, which describes 1:1 salts of this active pharmaceutical ingredient (API) with the two most widely used antifibrinolytic APIs, namely 6-aminohexanoic acid (aminocaproic acid, ACA) and tranexamic acid (TXA), which are zwitterions in the solid state. Since NSAIDs are known to cause adverse side effects such as gastrointestinal ulceration, the presence of ACA and TXA in the salts with S-(+)-ibuprofen might counter these effects via their ability to prevent excessive bleeding. The salts were prepared by both the liquid-assisted grinding method and co-precipitation and were characterized by X-ray powder diffraction and single-crystal X-ray diffraction, thermal analysis, Fourier transform infrared spectroscopy, and solubility measurements. The X-ray analyses revealed a high degree of isostructurality, both at the level of their respective asymmetric units and in their extended crystal structures, with charge-assisted hydrogen bonds of the type N-H+⋅⋅⋅O− and O-H+⋅⋅⋅O− featuring prominently. The thermal analysis indicated that both salts had significantly higher thermal stability than S-(+)-ibuprofen. Solubility measurements in a simulated biological medium showed insignificant changes in the solubility of S-(+)-ibuprofen when tested in the form of the salts (S-IBU)−(ACA)+ and (S-IBU)−(TXA)+.

Novel Pharmaceutical Cocrystals and Solvate Crystals of Nobiletin, a Citrus Flavonoid with Potent Pharmacological Activity.

Nobiletin (NOB) is a flavonoid with attractive pharmaceutical characteristics, including anti-Alzheimer's, anti-inflammation, and anti-cancer properties, but it has low solubility in water, resulting in reduced bioavailability. Its solubility must be improved to develop NOB as a drug. Cocrystal engineering can change the physicochemical properties of an active pharmaceutical ingredient and generate remarkable drug candidates that are superior in drug formulation. In this report, extensive co-crystal screening of NOBs with 31 cocrystal formers (coformers) with various functional groups was carried out by the liquid-assisted grinding method. As a result, four cocrystals (NOB with urea (URE), oxalic acid, gallic acid and salicylic acid) and one solvate crystal (NOB with formic acid (FOR)) were found. Powder X-ray diffraction and thermal analysis revealed the unique crystal morphology of all the obtained samples. In addition, the crystal structures of two of them (NOB-URE and NOB-FOR) were determined by single crystal X-ray diffraction. The results revealed that NOB-URE and NOB-FOR are new cocrystals or solvate crystals consisting of molar ratios of 1 : 2 and 1 : 0.73, respectively. In NOB-URE, we could observe a transient increase in solubility due to supersaturation, suggesting that URE is one of the better coformers of NOB.

Liquid-assisted mechanochemical synthesis, crystallographic, Hirshfeld surface and theoretical study for Nonlinear Optical (NLO) properties of novel copper complexes: Bis(2,9-dimethyl-1,10-phenanthroline)-copper perchlorate and bromidobis(1,10-phenanthroline)-copper

The two novel Cu (I) complexes, [Cu(dmp)2]ClO4 with 2,9-dimethylphenanthroline (dmp) and [Cu(phen)2Br] with 1,10-phenanthroline (phen) were synthesized by liquid assisted grinding (LAG) method followed by heating. Complexes were characterized by using SC-XRD, FT-IR and UV-Visible spectroscopic techniques. The complex (1) [Cu(dmp)2]ClO4 crystallized in the Orthorhombic with the space group P 21 21 21, a = 11.9229(2) Å, b = 12.4823(3) Å, c = 18.2499(3) Å and Complex (2) [Cu(phen)2Br] crystallized in the Monoclinic with the space group C2/c, a = 23.247(5) Å, b = 30.731 (6) Å, c = 7.5317(15) Å and β = 97.677(6)o. The FMOs study based on DFT showed the complex (2) has high value of chemical softness and more easily polarized compare to complex (1). The HOMO-LUMO energy gap in complex (2) is small compared to complex (1) due to which there is easier intramolecular charge transfer (ICT) in complex (2) which support the higher third order NLO (γ) response of the complex (2). The statistical calculations for Pearson correlation coefficient (r) and the P values showed that the selected level of theory is appropriate for the theoretical calculations of the complexes. Theoretical calculation showed that both the complexes have higher third order NLO response compared to prototypical urea.

Exploring the Crystal Structure Landscape of Sulfasalazine through Various Multicomponent Crystals.

Sulfasalazine is used as an anti-inflammatory drug to treat large intestine diseases and atrophic arthritis. In the solid state, two tautomers are known: an amide tautomer (triclinic polymorph) and an imide tautomer (monoclinic polymorph). Crystallization of six new multicomponent solids of sulfasalazine with three cocrystal formers and three salt formers has been achieved by slurry, liquid-assisted grinding and slow evaporation methods. All of the solid forms are characterized by X-ray diffraction techniques, thermal analysis, and Fourier transform infrared spectroscopy. The crystal structural analysis reveals that two sulfasalazine molecules or anions arrange in a head-to-head fashion involving their pyridyl, amide, and sulfonyl groups in an R22(7):R22(8):R22(7) motif. This is the key structural unit appearing in both sulfasalazine imide polymorph and all six multicomponent crystals. In addition, sulfasalazine exists in the amide form in all unsolvated multicomponent crystals obtained in this work and adopts the imide tautomer in the solvated cocrystals and salt. Hirshfeld surface analysis and the associated two-dimensional (2D) fingerprint plots demonstrate that sulfasalazine has significant hydrogen bond donor capability when cocrystallized and is a significant hydrogen bond acceptor in the salts. The frontier molecular orbital analysis indicates that sulfasalazine cocrystals are chemically more stable than the salts.

Study on preparation of pillararene cocrystals by liquid-assisted grinding

Liquid-assisted grinding (LAG) has received wide attention in chemical synthesis field. Here, we reported that LAG provides a smart strategy to build macrocyclic cocrystal (MCC), achieving quick modification. The macrocyclic cocrystal has been assembled by electronegative permethylated pillar[5]arenes (EtP5) and electropositive ligands. We select three ligands with strong electron-deficient groups for cocrystal preparation with EtP5 by LAG and judge whether the grinding products are cocrystals by color change, Infrared (IR), Ultraviolet-visible (UV-vis) absorption, and X-ray diffraction (XRD). We demonstrated that the same structure as solvent cocrystal can be obtained by LAG. We obtained the single crystal structure of the EtP5 cocrystal with the promising ligand, confirming the formation of cocrystals and the reliability of the liquid-assisted grinding method.

Mechanistic study of the increased phototoxicity of titanium dioxide nanoparticles to Chlorella vulgaris in the presence of NOM eco-corona

Widespread applications and release of photoactive nanoparticles (NPs) such as titanium dioxide (TiO2) into environmental matrices warrant mechanistic investigations addressing toxicity of NPs under environmentally relevant conditions. Accordingly, we investigated the effects of surface adsorbed natural organic matters (NOMs) such as humic acid, tannic acid and lignin on the band gap energy, abiotic reactive oxygen species (ROS) generation, surface chemistry and phototoxicity of TiO2 NPs. Initially, a liquid assisted grinding method was optimized to produce TiO2 NPs with a NOM layer of defined thickness for further analysis. Generally, adsorption of NOM reduced the band-gap energy of TiO2 NPs from 3.08 eV to 0.56 eV with humic acid, 1.92 eV with tannic acid and 2.48 eV with lignin. Light activated ROS generation by TiO2 NPs such as hydroxyl radicals, however, was reduced by 4, 2, 9 times in those coated with humic acid, tannic acid and lignin, respectively. This reduction in ROS despite decrease in band gap energy corroborated with the decreased surface oxygen vacancy (as revealed by X-ray Photoelectron Spectroscopy (XPS)) and quenching of ROS by surface adsorbed NOM. Despite the reduced ROS generation, the NOM-modified TiO2 NPs exhibited an increased phototoxicity to Chlorella vulgaris in comparison to pristine TiO2 NPs. Further analysis suggested that photoactivation of NOM modified TiO2 NPs releases toxic degradation products. Findings from our studies thus provide mechanistic insight into the ecotoxic potential of NOM-modified TiO2 NPs when exposed to light in the environment.

Mesomorphic and computational evaluation of C[tbnd]N‧‧‧I halogen bonded complexes of 4-alkoxy-4′-cyanobiphenyls systems with 1,6- diiodoperfluorohexane

Thermotropic halogen bonded (XB) liquid crystalline complex (A-n XB) of 4-alkoxy-4′- cyano biphenyls (A-n) systems containing nitrile (-CN) group with variable alkoxy chain length (-CnH2n+1, where n = 3 to 10) acting as halogen bond acceptor with 1,6-diiodoperfluorohexane, (I-atom) acting as halogen bond donor were prepared by the liquid-assisted grinding method. The A-n XB complex formations, through CN‧‧‧I XB interactions, were established by the FTIR, Raman, PXRD, polarizing optical microscope (POM) with hot stage, DSC and TGA techniques. Further, POM study of these homologous XB complex series showed liquid crystalline phases with a alteration of (1–10 °C) compared to their respective parent mesogenic molecules. The computational study was carried out using Frontier Molecular Orbitals (FMOs), Molecular Electrostatic Potential (MEP), Non-covalent interactions (NCI) and Quantum theory of atoms in molecule (QTAIM) analysis to evaluate the reactivity parameters and strength of XB in the complexes.

Computational and optoelectronic quantification of semi-conducting, warm ruby red color emanating Eu3+ complexes with hetro-cyclic ligands.

Six Eu3+ complexes were synthesised with β-keto acid as main ligand and secondary ligands through liquid assisted grinding method. These complexes were characterised by various techniques such as spectroscopic technique, XRD, EDAX, SEM analysis, thermal technique, Urbach energy and optical band gap investigation. The luminous photophysical properties were studied by PL spectroscopy in solid as well as solution phase and some theoretical calculation was done to investigate the radiative (Arad) & non-radiative (Anrad) transition rate, quantum efficiency (ɸ), Judd Ofelt parameters for 5D0 → 7F2,4 transitions in both states. Judd Ofelt parameters were also calculated by the JOES software and the outcomes are well harmonised with theoretical values. The complexes have CIE color coordinate value in ruby red region and above 88.65% color purity in both phases, which made them attractive candidates for red light-emitting displays. 5D0 → 7F2 transition was proposed as a laser emission transition owing to their high branching ratio (67.18-74.24%) in solid and (60.09-74.40%) in solution phase. Computational methods were employed to determine the structure and energy of various molecular orbitals. Antimicrobial assay of complexes was also rationalised and found that the complexes are pertinent as good bactericidal and fungicidal agents in pharmaceutical industry.

Synthesis and photo-physics of luminescent Sm(III) complexes derived from β-hydroxyketone and heterocyclic ancillary ligands

A series of six Sm (III) complexes containing organic ligands were synthesized using liquid assisted environment-friendly grinding method. The complexes were characterized through various techniques like UV, IR, NMR, XRD, SEM, EDAX, PL and TGA/DTG. The luminescent properties studies in solid and solution form suggests that 4G5/2 → 6H7/2 (604 nm) and 4G5/2 → 6H9/2 (645 nm) transitions were accountable for the orange and reddish orange emission respectively on UV excitation. An orange colour light emission is also consistent with the outcomes of chromaticity, i.e., colour coordinates, CCT, and CP. To know further about the coordination environment Judd-Ofelt intensity parameters (Ω2, Ω4, Ω6) were calculated. In complexes greater value of Ω2 in comparison to Ω4 and Ω6 is the result of greater covalence. The band gap and Urbach energy obtained lie in the range of semiconductor devices. The HOMO-LUMO gap obtained theoretically and experimentally are in agreement with each other. These complexes have potential application in laser devices. The evaluation of antioxidant and antimicrobial properties of complexes indicates their application in pharmaceutical industry.

Synthesis, Structural and Theoretical Analyses of C≡N···I Halogen-Bonded Liquid Crystalline Complexes of 4-Cyano-4′-alkoxy Biphenyl Systems

A series of 4-cyano-4′-alkoxybiphenyl compounds were synthesized by varying the spacer chain lengths (−CH2−)n, where n = 3–10, for the systematic study of a halogen-bonded (XB) complex with 1,4-diiodotetrafluoro benzene. The XB liquid crystalline complexes obtained from the liquid-assisted grinding method were characterized by FTIR, Raman, DSC, and PXRD studies. Further, C≡N···I XB interaction was established by single-crystal X-ray diffraction analysis. The odd-even analysis has suggested that the even carbon chain length containing XB liquid crystalline complexes shows slightly higher alteration in their isotropic temperature compared to the odd carbon chain lengths of such complexes. Furthermore, it is interesting to note that the higher alkyl chain complexes (n = 6–10) showed liquid crystalline temperature at lower values with respect to their ligands. The Hirshfeld and energy framework analyses have also been carried out to assess the stability and percentage contribution of XB noncovalent interaction. The frontier molecular orbital, noncovalent interaction, molecular electrostatic potential, and QTAIM analysis were performed using DFT to evaluate the nature of XB in these halogen-bonded liquid crystalline systems.

Exploration of various solid forms of novel (1H-Benzimidazole, 2-[4-(1,1-dimethylethyl) phenyl

Polymorphism/solid forms are acknowledged to have important implications in the pharmaceutical industry, hence regulating polymorph/solid forms formation is essential. 1H-Benzimidazole, 2-[4-(1,1-dimethylethyl)phenyl] (BDP) drug has been discovered as a transcriptional activator of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in certain metabolic tissues. Up to date, there is no solid forms of BDP have been reported. The purpose of this study was to see how changing solvent conditions and co-formers influenced the formation of distinct solid forms of BDP. The solvents were chosen based on their polarity, as different polarity solvents are anticipated to interact differently with APIs, impacting the creation of diverse solid forms. Similarly, two GRAS (Generally Recognized As Safe) co-formers, Oxalic Acid (OA) and Malonic Acid (MA), were employed to test the potential of various forms of BDP to form diverse supramolecular networks that might improve BDP's physicochemical qualities. The experimental finding reveals that one polymorph, two solvates and three molecular salts have been obtained by solvent evaporation (SE) and liquid assisted grinding (LAG) methods. Interestingly, BDP creates a similar channel structure in all the two solvates (acetone and isopropanol). Furthermore, different forms of BDP using the same co-former show different molecular assemblages, confirming the occurrence of multiple forms. PXRD, SCXRD, and thermal analyses were used to characterize all of the synthesized forms. The findings of this study indicate that solvent choice and synthesis process are important factors in polymorph screening and can influence the creation of diverse molecular forms.

Rucaparib cocrystal: Improved solubility and bioavailability over camsylate

Rucaparib (Ruc) is a drug used to treat advanced ovarian cancer associated with deleterious BRCA mutations. Its commercial form, the camsylate salt (Ruc-Cam), suffers from poor aqueous solubility and thus causes low and erratic oral bioavailability. In this work, we aimed to improve the oral exposure of Ruc through cocrystallization. Liquid-assisted grinding, slurry, and solvent evaporation methods were employed to prepare new solid forms of Ruc. Cocrystals of rucaparib-theophylline monohydrate (Ruc-Thp MH), rucaparib-maltol (Ruc-Mal), and rucaparib-ethyl maltol (Ruc-Emal) were obtained. Powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and dynamic vapor sorption were utilized to characterize these multi-component systems. All cocrystals dissolve faster than Ruc-Cam at pH 2.0 and 4.5, and Ruc-Thp MH displays the highest apparent solubility in pH 4.5 and 6.8 buffers. Pharmacokinetic studies in rats show that Ruc-Thp MH exhibits 2.4 times the Cmax and 1.4 times the AUC0-24h at a single dose compared with Ruc-Cam. The enhanced solubility and bioavailability of Ruc-Thp MH showcase the power of cocrystallization in addressing absorption issues in drug development.

Pharmaceutical Co-crystal of Antiviral Agent Efavirenz with Nicotinamide for the Enhancement of Solubility, Physicochemical Stability, and Oral Bioavailability.

The present research work attempted to improve the oral bioavailability of the antiviral drug Efavirenz (EFV) using a pharmaceutical cocrystallization technique. EFV comes under BCS-II and has extremely low water solubility, and results in low oral bioavailability. EFV and nicotinamide (NICO) were selected in a (1:1) stoichiometric ratio and efavirenz nicotinamide cocrystal (ENCOC) was prepared through the liquid-assisted grinding method (LAG). The confirmation of the formation of a new solid phase was done through spectroscopic techniques like Fourier transmission infrared (FTIR), Raman, and 13C solid-state nuclear magnetic resonance (13C ssNMR). Thermal techniques like differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and hot stage microscopy (HSM) illustrated the thermal behavior and melting patterns of ENCOC, EFV, and NICO. The X-ray powder diffraction (XRPD) confirms the formation of a new crystalline phase in ENCOC. The Morphology was determined through scanning electron microscopy (FESEM). The results of saturated solubility studies andin vitro drug release studies exhibited 8.9-fold enhancement in solubility and 2.56-fold enhancement in percentage cumulative drug release. The percentage drug content of ENCOC was found higher than 97% and cocrystal exhibits excellent accelerated stability. The oral bioavailability of EFV (Cmax, 799.08ng/mL) exhibits significant enhancement after cocrystallization (Cmax, 5597.09ng/mL) than EFV and Efcure®-200 tablet (2896.21ng/mL). The current work investigates the scalable and cost-effective method for enhancement of physicochemical stability, solubility, and oral bioavailability of an antiviral agent EFV.

Preparation of Atorvastatin Calcium-Dipicolinic Acid Multicomponent Solids by Liquid-Assisted Grinding Method to Increase Solubility

Atorvastatin calcium is a cholesterol-lowering drug that is very potent but difficult to dissolve in water, so its bioavailability is low. In this study, atorvastatin calcium-dipicolinic acid multicomponent solids were prepared using the liquid-assisted grinding method to improve atorvastatin calcium's solubility. Characterization of multicomponent solids was carried out using powder x-ray diffraction (PXRD), differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Solubility test was carried out by shaking method using distilled water media. The results showed that the particles of atorvastatin calcium - dipicolinic acid multicomponent solids had an irregular shape with rough and porous surface topography. The multicomponent solids have a diffractogram with specific peaks of 2θ at 8.8, 9.9, 11.5, 16.7, 19.1, 21.2, 22.4, 23.4, and 27.7°. The DSC thermogram of multicomponent solids showed a sharp endothermic peak at 181.9 °C (∆H=17.69 J/g), indicating its melting point. The FTIR spectra of atorvastatin calcium-dipicolinic acid multicomponent solids indicated an intermolecular interaction that was thought to be a hydrogen bond between the molecules of atorvastatin calcium and dipicolinic acid. The results of the solubility test showed that the atorvastatin calcium-dipicolinic acid multicomponent solids had a significantly increased solubility (p<0.05) compared to the solubility of pure atorvastatin calcium.

Synthesis of {P2W18}-based coated structured nano materials with supercapacitors and H2O2 sensing

The combination of metal-organic frameworks (MOFs) with large specific surface area and high stability and Dawson-type polyoxometalates (POMs) with excellent electron transfer ability to build a new inorganic-organic hybrid as energy storage materials can give full play to the advantages of both. Therefore, the inorganic organic hybrid nano material {Ag4K2P2W18O62}@[Ag3(μ-Hbtc)(μ-H2btc)]n (which became {Ag4K2P2W18O62}@Ag-BTC, where BTC = 1,3,5-benzenetricarboxylic acid) was synthesized by liquid-assisted grinding. The XRD, SEM, TEM characterization show that {Ag4K2P2W18O62}@Ag-BTC is a coating structure. The specific capacitance is 378.9 F g−1 at a current density of 1 A g−1, with a retention rate of 93.5 % for 5000 cycles. An energy density of 7.8 Wh kg−1 and the power density of 500.0 W kg−1 are obtained in water-based symmetric two-electrode supercapacitor system. In addition, when used as an H2O2 sensor, it has a broad detection range of 1.5 μM to 1.5 mM and the small detection limit of 0.206 μM, also offers excellent interference immunity and stability. Moreover, by applying this nano material to the detection of H2O2 in human serum, results are acceptable. The above result shows that the composite material synthesized by the liquid-assisted grinding method adequately combines properties of both parent materials is a viable strategy for achieving performance enhancement.

Study of Judd-Ofelt, Urbach energy and photosensitization process in luminescent Sm(III) complexes with heterocyclic ligands.

Six samarium (III) complexes were synthesised by employing the β-ketocarboxylic acid as main ligand and five N-donor systems as ancillary ligands through the environmentally safe liquid-assisted grinding method. Various characterisation techniques were employed to determine the structure of the complexes i.e. NMR, IR, XRD and SEM. Photoluminescent studies were carried out in solid as well as in solution form. In solid and solution form emission spectra show maximum intensity peak at 604 and 602nm, respectively, assigned to 4G5/2 → 6H7/2 transition which explains orange emission on UV excitation in complexes. CCT, CP, colorimetric parameters and quantum yield (relative and intrinsic) of the synthesized complexes were calculated. With the help of reflectance spectra, band gap and Urbach energy were determined. Lasing parameters were also calculated by employing FWHM values obtained from Gaussian fitting. Energy transfer study revealed the efficacious energy transfer from ligand to metal's emissive level. Further antimicrobial studies revealed higher activity in case of complexes in comparison to ligand.

Investigation into the structures and physicochemical properties of multi-component crystals of voriconazole

Voriconazole (VZL) is a second-generation and broad-spectrum triazole against fungal infections. Being a BCS (biopharmaceutics classification system) class II compound, the poor aqueous solubility has limited its bioavailability and clinical efficacy. Aims to overcome this disadvantage, a cocrystallization strategy based on crystal engineering principles has resulted in five new multi-component crystals of VZL with maleic acid, L-tartaric, protocatechuic, gallic, and 3,5-dinitrobenzoic acids. Structure analysis revealed that the hydroxyl/carboxylic acid•••triazole N 3 hydrogen bonding interaction appears as a main supramolecular heterosynthon in the VZL multi-component crystals with organic acids. And VZL molecule has a flexible conformation in each of the five multi-component structures. The newly synthesized multi-component crystals showed impressive solubility improvement compared to that of the raw material of VZL. Molecular electrostatic potential surfaces (MEPS) analysis based on density functional (DFT) calculations revealed that hydrogen bond interactions in cocrystals mainly involved pairwise interactions in the global maxima and minima sites, but this rule is not always followed. This study indicates the potential of cocrystals to improve the solubility and dissolution rate of VZL Novel voriconazole multi-component crystals were prepared via liquid-assisted grinding and solvent evaporation method. Cocrystallization technique shows impressive advantages in improving the solubility and dissolution rate of voriconazole.