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The design mebendazole (MBZ) multicomponent systems is important to obtain new materials that incorporate the API (active pharmaceutical ingredient) with better thermal stability, avoiding the interconversion of desmotropes. Interestingly, the presence of water molecules in the mebendazolium mesylate monohydrate prevents the formation of the R22(8) supramolecular synthon, found in all mebendazolium salts with polyatomic counterions. Here, we designed a new mebendazolium mesylate anhydrous salt based on statistical scrutiny of all mebendazole crystal structures identified in the literature and an exhaustive analysis of the conformational and geometrical requirements for the supramolecular assembly. The synthesis of this new salt and its solid-state characterization through single-crystal X-ray diffraction and complementary techniques are presented. As expected, mebendazole recrystallization in methanol with methanesulfonic acid - a Food and Drug Administration accepted coformer - in the absence of water yields a mesylate anhydrous salt with 1 : 1 stoichiometry. This new salt crystallizes in the P212121 (19) space group. The main intermolecular interactions found in the crystal structure are the hydrogen bonds that form a R22(8) supramolecular motif that assembles the ionic pairs. Additional non-classical H-bond, as well as π⋯π and carbonyl⋯cation interactions, contribute to the final stabilization of the crystal packing. This new salt is stable up to 205 °C when it undergoes the endothermic loss of the ester moiety to yield 2-amino-5-benzoylbenzimidazole. Moreover, preliminary dissolution experiments in aqueous 0.1 mol L-1 HCl suggest an apparent solubility of mebendazolium mesylate anhydride 2.67 times higher than that of the preferred for pharmaceutical formulations MBZ form C.

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Famotidine (FMT) is an orally administered histamine H2-receptor blocker with limited bioavailability since it exhibits low solubility and low permeability. In addition, the recent withdrawal of ranitidine from the market, makes famotidine an interesting candidate to obtain solid forms with improved pharmacokinetic performance. In this work, crystal engineering concepts and the co-amorphous formation strategy were applied to obtain two novel solids. Crystalline famotidine malate (FMT-MT) and a vitreous phase (FMT-MTa) were prepared by solvent evaporation and mechanochemical synthesis, respectively. FMT-MT (monoclinic, S.G. P21/n) crystallizes with one FMT and one co-former molecules in the asymmetric unit forming a (R228) structural motif. FMT-MT resulted in a salt by proton transfer from one malic carboxylic group to the guanidine moiety of FMT. The three-dimensional packing is described as undulating layers of alternated FMT+ and MT- running along the a direction. FMT-MTa shows the inherent features of amorphous phases according to powder X-ray diffraction and DSC analysis. The higher physical stability was found for amorphous samples maintained at 4 °C up to 60 days. The solubility assays in water, indicate that FMT-MT and FMT-MTa are 2.02 and 2.68-fold more soluble than the marketed polymorph, whereas similar values were obtained in simulated gastric fluid.

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In this work, the influence of degassing temperature and urea functionalization were investigated as ways to improve the CO2 adsorption performance of CPO-27-Mg. Through post-synthesis modification treatments, four samples with different degrees of urea functionalization were obtained, incorporating 10, 25, 50, and 100% of urea concerning the metal sites of the MOF. Alternatively, the influence of the degassing temperature of the non-functionalized MOF between 70 and 340 °C was also evaluated. The resulting compounds were characterized by N2 adsorption-desorption isotherms at -196 °C using TGA-MS, FTIR, and PXRD. Finally, the thermally treated and functionalized CPO-27-Mg was evaluated for CO2 capture.

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Water-ethanol suspensions of 2D coordination network (CN) based on rare earth elements and mixed ligands were evaluated as reactive oxygen species (ROS) generators under UV light irradiation, in contact with a biomimetic substrate (tryptophan) or an O2(1Δg) quencher (1,3-diphenylisobenzofuran; 1,3-DPBF). A combination of bottom-up and top-down strategies was implemented in order to obtain nano-sized CN particles and the subsequent colloidal suspensions were also tested towards photodynamic inactivation of Candida albicans (C. albicans). SEM, TEM, FTIR, and XRD techniques were applied to characterize the solids and ICP-AES was employed to determine the metal content of the colloidal suspensions. Promising results were found indicating that the presence of Tb3+ allows an intersystem crossing suitable for singlet oxygen generation, resulting in the antifungal activity of C. albicans culture upon UV-irradiation.

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Drug encapsulation in nanocarriers such as polymeric nanoparticles (Nps) may help to overcome the limitations associated with cannabinoids. In this study, the authors' work aimed to highlight the use of electrospraying techniques for the development of carrier Nps of anandamide (AEA), an endocannabinoid with attractive pharmacological effects but underestimated due to its unfavourable physicochemical and pharmacokinetic properties added to its undesirable effects at the level of the central nervous system. The authors characterised physicochemically and evaluated in vitro biological activity of anandamide/ɛ-polycaprolactone nanoparticles (Nps-AEA/PCL) obtained by electrospraying in epithelial cells of the human proximal tubule (HK2), to prove the utility of this method and to validate the biological effect of Nps-AEA/PCL. They obtained particles from 100 to 900 nm of diameter with a predominance of 200-400 nm. Their zeta potential was -20 ± 1.86 mV. They demonstrated the stable encapsulation of AEA in Nps-AEA/PCL, as well as its dose-dependent capacity to induce the expression of iNOS and NO levels and to decrease the Na+/K+ ATPase activity in HK2 cells. Obtaining Nps-AEA/PCL by electrospraying would represent a promising methodology for a novel AEA pharmaceutical formulation development with optimal physicochemical properties, physical stability and biological activity on HK2 cells.

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Two lanthanide doped nanosystems Ca0.8Ln0.1Na0.1WO4 (Ln = Eu, Sm), denoted as Eu@CWO and Sm@CWO, were prepared by a "top-down" approach in three simple steps: activation, miniaturization by high-energy milling, and further calcination. The solids were thoroughly characterized by X-ray powder diffraction (XRPD) and Scanning-electron microscopy (SEM). Also, analyses of the structure of the compounds and the impact of milling on the crystallite shape and size were carried out through Rietveld refinements. Solid-state photoluminescence was studied in terms of excitation, emission, lifetimes (τobs) and europium-quantum yields. Finally, the Eu@CWO sample was employed as a potential water-stable chemical sensor towards toxic cations, showing a quenching effect in the presence of iron ions.

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Famotidine (FMT) and ibuprofen (IBU) were used as model drugs to obtain coamorphous systems, where the guanidine moiety of the antacid and the carboxylic group of the nonsteroidal anti-inflammatory drug could potentially participate in H-bonds leading to a given structural motif. The systems were prepared in 3:7, 1:1, and 7:3 FMT and IBU molar ratios, respectively. The latter two became amorphous after 180 min of comilling. FMT-IBU (1:1) exhibited a higher physical stability in assays at 4, 25, and 40 °C up to 60 days. Fourier transform infrared spectroscopy accounted for important modifications in the vibrational behavior of those functional groups, allowing us to ascribe the skill of 1:1 FMT-IBU for remaining amorphous to equimolar interactions between both components. Density functional theory calculations followed by quantum theory of atoms in molecules analysis were then conducted to support the presence of the expected FMT-IBU heterodimer with consequent formation of a R228 structural motif. The electron density (ρ) and its Laplacian (∇2ρ) values suggested a high strength of the specific intermolecular interactions. Molecular dynamics simulations to build an amorphous assembly, followed by radial distribution function analysis on the modeled phase were further employed. The results demonstrate that it is a feasible rational design of a coamorphous system, satisfactorily stabilized by molecular-level interactions leading to the expected motif.

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Mixing aqueous solutions of sodium diclofenac (DIC-Na) and ranitidine hydrochloride (RAN·HCl) afforded an off-white solid (DIC-RAN) that was investigated from the microscopic, thermal, diffractometric, spectroscopic, and functional (chemometrics-assisted dissolution) points of view. The solid has a 2:1 (DIC:RAN) molar ratio according to (1)H nuclear magnetic resonance spectroscopy. It is thermally stable, displaying a broad endothermic signal centered at 105°C in the thermogram, and its characteristic reflections in the powder X-ray diffractogram remained unchanged after a 3-month aging period. Scanning electron microscopy micrographs uncovered its morphology, whereas the spectral data suggested an interaction between the carboxylic acid of DIC and the alkyldimethylamino moiety of RAN. The dissolution of DIC-RAN was monitored at different pH values by an ultraviolet/chemometrics procedure, being complete within 5 min at pH 6.8. This compares favorably with the dissolution of a DIC-Na sample of the same particle size.

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In this paper, co-grinding mixtures of omeprazole-amoxicillin trihydrate (CGM samples) and omeprazole-anhydrous amoxicillin (CGMa samples) at 3:7, 1:1 and 7:3 molar ratios, respectively, were studied with the aim of obtaining a co-amorphous system and determining the potential intermolecular interactions. These systems were fully characterized by differential scanning calorimetry (DSC), FT-infrared spectroscopy (FTIR), X-ray powder diffraction (PXRD), scanning electron microscopy (SEM) and solid state Nuclear Magnetic Resonance (ssNMR). The co-grinding process was not useful to get a co-amorphous system but it led to obtaining the 1:1 CGMa disordered phase. Moreover, in this system both FTIR and ssNMR analysis strongly suggest intermolecular interactions between the sulfoxide group of omeprazole and the primary amine of amoxicillin anhydrous. The solubility measurements were performed in simulated gastric fluid (SGF) to prove the effect of the co-grinding process. Complementarily, we carried out density functional theory calculations (DFT) followed by quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses in order to shed some light on the principles that guide the possible formation of heterodimers at the molecular level, which are supported by spectroscopic experimental findings.

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The characterization of the inclusion complex between 2-hydroxybenzophenone (2OHBP) and ß-cyclodextrin (ßCD) in the solid state was performed using Fourier transform infrared spectroscopy (FTIR), powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and transmission electron microscopy (TEM). The apparent formation constant of the complex was determined by phase solubility diagrams and liquid chromatography (HPLC) at different temperatures. The formation of the inclusion complex induced slight shifts in the FTIR spectrum while by PXRD a new crystalline phase was observed. TEM studies revealed that the complex forms aggregates of nanometric size. The inclusion complex showed a higher solubility in the tested dissolution media than free 2OHBP. Moreover, the freeze-dried solid complex exhibits a higher thermal stability than the solid free drug. The thermodynamic analysis allowed us to conclude that the encapsulation process is endothermic in water and exothermic in methanol-water.

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Famotidine (FMT), a histamine H2 -receptor antagonist, is a drug commonly used in treatments of gastroesophageal diseases that presents solid-state polymorphism (A and B forms), the marketed form being the metastable polymorph B. A new stable salt was obtained by combination of FMT and maleic acid as coformer. FMT maleate (FMT-MLT) was prepared either by solvent evaporation or comilling methods. Single-crystal X-ray diffraction reveals that (FMT)(+) in FMT-MLT adopts an extended conformation that is stabilized by classical and nonclassical H-bonds. The three-dimensional packing consists of tapes along the axis b that further develop a columnar array based on H-bonds involving (FMT)(+) side chain. Nonconventional π-stacking interactions between adjacent tapes were also identified. Fourier transform infrared, differential scanning calorimetry, thermogravimetric analysis, polarized light thermal microscopy, and scanning electron microscopy were employed to characterize the multicomponent complex. According to the solubility values in water and simulated gastric fluid, FMT-MLT exhibits such a performance that improves on the solubility of the commercially available polymorph. Finally, the higher stability of FMT-MLT regarding both FMT forms, as well as its easy preparation from either A or B forms or a mixture of them, also allows to consider this salt as a valuable alternative to avoid the polymorphism issue in marketed formulations containing FMT.

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Mebendazole mesylate monohydrate, a new stable salt of mebendazole (MBZ), has been synthesized and fully characterized. It was obtained from recrystallization of MBZ forms A, B, or C in diverse solvents with the addition of methyl sulfonic acid solution. The crystal packing is first organized as a two-dimensional array consisting of rows of alternating MBZ molecules linked to columns of mesylate ions by hydrogen bonds. The three-dimensional structure is further developed by classical intermolecular interactions involving water molecules. In addition, nonclassical contacts are also found. The vibrational behavior is consistent with the crystal structure, the most important functional groups showing shifts to lower or higher frequencies in relation to the MBZ polymorphs. Thermal analysis indicates that the compound is stable up to 50°C. Decomposition occurs in five steps. Solubility studies show that the title compound presents a significant higher performance than polymorph C. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:3528-3538, 2013.

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Two new holmium-succinate frameworks have been synthesized by hydrolysis in situ of the succinylsalicylic acid under different hydrothermal conditions. Compound 1, [Ho(2)(C(4)H(4)O(4))(3)(H(2)O)(2)]·0.33(C(7)H(6)O(3)), P ̅i space group, has a novel structure composed by 1D-SBUs consisting of [HoO(9)] chains of polyhedra linked by the succinate ligands giving a 3D framework. Compound 2, [Ho(2)(C(4)H(4)O(4))(3)(H(2)O)(2)], also belonging to the P ̅i space group, has a denser structure. The role of the in-situ-generated salicylic acid on formation of both structures is studied by means of a synthesis design methodology. A topological study of the new holmium succinate compounds in comparison with the previously reported 3D holmium-succinate framework is performed here.

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Two new layered polymeric frameworks have been synthesized under different hydrothermal conditions and characterized by single-crystal X-ray diffraction, thermal analysis, and variable temperature-Fourier Transform Infrared Spectroscopy (VT-FTIR). The compound I, with formula [Er(2)(dms)(3)(H(2)O)(4)], has a triclinic cell with parameters a = 5.8506 A, b = 9.8019 A, c = 11.9747 A, alpha = 70.145 degrees , beta = 80.234 degrees , and gamma = 89.715 degrees , and the compound II, [Er(2)(dms)(3)(H(2)O)], is monoclinic and its cell parameters are a = 11.1794 A, b = 18.2208 A, c = 12.7944 A, beta = 112.4270 degrees , where dms = 2,2-dimethylsuccinate ligand. A theoretical study including energy calculations of the dms conformers was carried out at the Density Functional Theory (DFT-B3LYP) level of theory, using the 6-311G* basis set. Further calculations of the apparent formation energies of I and II crystalline structures were performed by means of the periodic density functional theory, using DF plane-waves. The analysis of the structural features, theoretical relative stabilities, and the influence of synthesis conditions are presented here. The heterogeneous catalytic activity of the new compounds is tested and reported.

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Se presenta por primera vez un estudio sobre la frecuencia de litiasis urinaria en la ciudad de San Luis, Argentina, a partir de datos de espectroscopía infrarroja. Se analizaron los espectros infrarrojos de 169 cálculos urinarios provenientes de centros sanitarios tanto públicos como privados. Los componentes químicos encontrados fueron oxalato de calcio monohidrato, uratos, fosfato de calcio, fosfato amónico magnésico hexahidrato y de composición mixta. El análisis cuantitativo de los datos, utilizando la estadística descriptiva, permitió determinar el tipo de composición litiásica más frecuente en el total de los sujetos y la distribución de los tipos encontrados según sexo y edad. La frecuencia de oxalato de calcio monohidrato y de uratos fue mayor en hombres que en mujeres correspondiendo a una franja etaria entre 21 y 60 años y entre 41 y 70 años, respectivamente. Esta relación se invierte en los fosfatos de calcio o magnesio presentando mayor incidencia en mujeres. Los cálculos de composición mixta se distribuyen de igual manera entre hombres y mujeres.

A study dealing with urinary lithiasis frequency in San Luis city, Argentina, applying infrared spectroscopy is reported for the first time. The infrared spectra of 169 urinary stones provided by public and private sanitary centers were analyzed. The most frequent chemical components found were calcium oxalate monohydrate, urates, calcium phosphate, magnesium ammonium phosphate hexahydrate and mixed compositions. Quantitative data analysis, performed by descriptive statistics enabled the determination of the most frecuent lithiasic composition for all the cases, as well as its distribution according to the corresponding age and sex. Calcium oxalate monohydrate and urates were more frequently found in men than in women ranging between 21- 60 and between 41-70 years old, respectively. The inverse ratio is determined for calcium or magnesium phosphates, women being the most affected. Stones with mixed composition showed the same incidence in women and men.

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Yb(C(4)H(4)O(4))(1.5)] undergoes a temperature-triggered single-crystal to single-crystal transformation. Thermal X-ray single-crystal studies showed a reversibly orchestrated rearrangement of the atoms generated by the breaking/formation of coordination bonds, in which the stoichiometry of the compound remains unchanged. The transformation occurs on heating the crystal at approximately 130 degrees C. This uncommon behavior was also studied by thermal methods, FTIR spectroscopy, and thermodiffractometry. Both polymorphs, alpha (room-temperature form) and beta (high-temperature form), are proven to be active heterogeneous catalysts; the higher catalytic activity of beta is owed to a decrease in the Yb coordination number. A mechanism based on spectroscopic evidence and involving formation of the active species Yb-O-OH is proposed for the sulfide oxidation.

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Mebendazole (MBZ) is a common benzimidazole anthelmintic that exists in three different polymorphic forms, A, B, and C. Polymorph C is the pharmaceutically preferred form due to its adequated aqueous solubility. No single crystal structure determinations depicting the nature of the crystal packing and molecular conformation and geometry have been performed on this compound. The crystal structure of mebendazole form C is resolved for the first time. Mebendazole form C crystallizes in the triclinic centrosymmetric space group and this drug is practically planar, since the least-squares methyl benzimidazolylcarbamate plane is much fitted on the forming atoms. However, the benzoyl group is twisted by 31(1) degrees from the benzimidazole ring, likewise the torsional angle between the benzene and carbonyl moieties is 27(1) degrees. The formerly described bends and other interesting intramolecular geometry features were viewed as consequence of the intermolecular contacts occurring within mebendazole C structure. Among these features, a conjugation decreasing through the imine nitrogen atom of the benzimidazole core and a further resonance path crossing the carbamate one were described. At last, the X-ray powder diffractogram of a form C rich mebendazole mixture was overlaid to the calculated one with the mebendazole crystal structure.

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The role of citric acid in the demineralization of dental enamel, which is mainly constituted by hydroxyapatite, is important for periodontal regeneration and in the conditioning of enamel or dentin for bonding restorative resins. The adsorption of citric acid from aqueous solutions onto synthetic hydroxyapatite at 278, 288, 298, and 308 K and pH 4.8 has been studied by means of UV spectroscopy. The adsorption reaction, which takes place by an interaction between phosphate groups and citrate anions at the solid-solution interface, yields an adsorbate-adsorbent complex of high stability. The adsorption isotherms fit the Langmuirian shape. The proposed adsorption model, where citrate species interact in a bidentate manner (one citrate ion links two phosphate sites), is coherent with the experimental data. The activation standard heat and activation standard entropy were calculated. All the thermodynamic and kinetic parameters were in concordance with the adsorption reaction proposed in this work.