Polymorphism: an evaluation of the potential risk to the quality of drug products from the Farmácia Popular Rede Própria

O polimorfismo em sólidos é um fenômeno frequente em fármacos e pode levar a problemas na qualidade dos medicamentos por alterar suas propriedades físico-químicas, em especial a solubilidade e, consequentemente, a biodisponibilidade. Nesse trabalho realizou-se levantamento bibliográfico sobre os principais estudos e problemas relacionados ao polimorfismo em fármacos presentes nos medicamentos disponibilizados pela Farmácia Popular do Brasil. O polimorfismo deve ser controlado a fim de evitar possível ineficácia terapêutica e/ou dosagem inapropriada dos medicamentos. Destacamos que são poucos os ensaios obrigatórios para identificação e controle desse fenômeno em medicamentos, o que pode acarretar grande problema de saúde pública.Polymorphism in solids is a common phenomenon in drugs, which can lead to compromised quality due to changes in their physicochemical properties, particularly solubility, and, therefore, reduce bioavailability. Herein, a bibliographic survey was performed based on key issues and studies related to polymorphism in active pharmaceutical ingredient (APIs) present in medications from the Farmácia Popular Rede Própria. Polymorphism must be controlled to prevent possible ineffective therapy and/or improper dosage. Few mandatory tests for the identification and control of polymorphism in medications are currently available, which can result in serious public health concerns

Physical-chemistry study of the Brazilian ilmenites developing on a mafic pedosystem

Para determinar a composição química e os parâmetros cristalográficos da ilmenita, um óxido duplo de ferro e titânio, mineral normalmente descrito por meio de sua fórmula estequiométrica (FeTiO3), foi estudado um perfil de solo, desenvolvido de anfibolito. Neste trabalho, o mineral em questão, retirado da rocha fresca e alterada, bem como dos respectivos horizontes A, B e C do solo, foi estudado por difratometria de raios X, espectroscopia Mössbauer, medidas de magnetização espontânea e análise química. Procurando estabelecer relações entre a litologia de origem e a composição química e mineralógica das ilmenitas estudadas, foram também analisadas amostras provenientes de um Latossolo- Roxo, desenvolvido de basalto. Os resultados demonstram que em anfibolitos e solo dele derivado, a exemplo de outras rochas máficas, como o basalto e seus produtos de alteração, a espécie mineralógica, normalmente, relatada como ilmenita, com composição FeTiO3, é na verdade membro da série substitucional (1-x)Fe2O3(x)FeTiO3, com x variando de 0,79 a 0,91. Este mineral, quando no solo, é encontrado dentro de lamelas de espécies magnéticas (maghemita) e também na forma livre, na fração granulométrica do solo de tamanho do silte. Os resultados permitem ainda, verificar que, com o transcorrer do intemperismo, a solução sólida perde Fe3+, por mecanismos desconhecidos, tendendo sua composição para a da ilmenita estequiométrica.To determine the chemical composition and crystallographic parameter of ilmenite, a double oxide of iron and titanium, mineral normally described by its stoichiometric formula (FeTiO3), a soil profile developed from amphibolite has been studied. In this dissertation, the mineral at hand, it has taken from fresh and altered rock, and A, B, and C soil horizons. It has been studied by diffraction X-ray, Mössbauer spectroscopy, measurements spontaneous magnetic, and chemical analysis. In order to correlate the pedosystem lithology to the chemical composition and the ilmenites properties, it was also studied samples from Dusk Red Oxisols, developed from basalt. The present results show that ilmenites from anphibolite and derived soils as well as that from mafic rock and its soils are better described as a solid solution lying in the series (1-x)Fe2O3(x)FeTiO3, with 0.79 ≤ x ≤ 0.91. This mineral was found either in lamellae of soil and rock maghemite or free in soil silt fraction. The result shows that the mineral somehow loses Fe3+ during weathering tending to a final composition of stoichiometric ilmenite.Coordenação de Aperfeiçoamento de Pessoal de Nível Superio

Structure, Solubility and Stability of Orbifloxacin Crystal Forms: Hemihydrate versus Anhydrate

Orbifloxacin (ORBI) is a widely used antimicrobial drug of the fluoroquinolone class. In the official pharmaceutical compendia the existence of polymorphism in this active pharmaceutical ingredient (API) is reported. No crystal structure has been reported for this API and as described in the literature, its solubility is very controversial. Considering that different solid forms of the same API may have different physicochemical properties, these different solubilities may have resulted from analyses inadvertently carried out on different polymorphs. The solubility is the most critical property because it can affect the bioavailability and may compromise the quality of a drug product. The crystalline structure of ORBI determined by SCXRD is reported here for the first time. The structural analysis reveals that the ORBI molecule is zwitterionic and hemihydrated. ORBI hemihydrated form was characterized by the following techniques: TG/DTA, FTIR-ATR, and PXRD. A second crystalline ORBI form is also reported: the ORBI anhydrous form was obtained by heating the hemihydrate. These ORBI solid forms were isomorphous, since no significant change in unit cell and space group symmetry were observed. The solid-state phase transformation between these forms is discussed and the equilibrium solubility data were examined in order to check the impact of the differences observed in their crystalline structures

A pentacyclic triterpene from Maytenus imbricata: structure elucidation by X-ray crystallography

A pentacyclic triterpene, 3β,30-dihydroxy-lup-20(29)-ene, was isolated from the powder extract of Maytenus imbricata. The structure and stereochemistry of the compound were established by spectroscopic techniques and unambiguously determined by single crystal X-ray crystallography. The crystal structure shows one molecule in the asymmetric unit. The crystal packing is stabilized by O–H···O intermolecular hydrogen bonds, which give rise to infinite helical chains along the c unit cell axis. The intra-molecular geometry was analyzed using MOGUL, a knowledge base of molecular geometry derived from the Cambridge Structural Database (CSD)

Structural Invariance of a ZnII Coordination Polymer with 5-Aminoisophthalic Acid under Different Synthetic Conditions

<div><p>A same coordination polymer [Zn(aip)(DMSO)] (aip: 5-aminoisophthalate and DMSO: dimethylsulfoxide) was synthesized using the same reactants (ZnSO4, aip and H2O/DMSO) but in different conditions, in which the stoichiometry (1:1-4:1 metal:ligand ratio), temperature (70 and 100 °C) and synthetic method (liquid-liquid diffusion, solvothermal and conventional with stirring) varied. A liquid assisted mechanochemical approach using ZnO as ZnII source instead ZnSO4, but keeping DMSO as milling liquid, also resulted in the same compound. This new coordination polymer was investigated using single-crystal X-ray diffraction technique, revealing a two-dimensional honeycomb-type network formation. The crystal structure was compared with either similar or isostructural compounds reported in the literature. Our studies show that the synthetic method and other synthetic variables do not affect the formation of [Zn(aip)(DMSO)] coordination polymers and probe the high stability (thermodynamic and kinetic) and structural invariance of this structure.</p></div

Synthesis and characterization of the atropisomeric relationships of a substituted N-phenyl-bipyrazole derivative with anti-inflammatory properties

This work describes the atropisomeric relationships of 3-methyl-5-(3-methyl-5-phenyl-1H-pyrazol-1-yl)-1-phenyl-1H-pyrazol-4-amine (2d), which belongs to series 4-aminobipyrazole derivatives designed as anti-inflammatory agents. The 1H nuclear magnetic resonance spectra obtained in the presence of a chiral lanthanide shift salt associated to chiral high-performance liquid chromatography analysis, X-ray diffraction, and molecular modeling tools confirmed that ortho bis-functionalized bipyrazole 2d exists as a mixture of aR,aS-atropisomers. These results provide useful information to understand the pharmacological profile of this derivative and of other 4-aminobipyrazole analogs. Chirality 24:463470, 2012. (c) 2012 Wiley Periodicals, Inc.CAPES (BR.)CAPES (BR.)CNPq (BR.)CNPq (BR.)FINEP (BR.)FINEP (BR.)FAPERJ (BR.)FAPERJ (BR.

Non-centrosymmetric crystals of new N-benzylideneaniline derivatives as potential materials for non-linear optics

Three new N-benzylideneaniline derivatives [p-nitrobenzylidene-p-phenylamineaniline (I), 2,4-dinitrobenzylidene-p-phenylamineaniline (II) and p-dinitrobenzylidene-p-diethylamineaniline (III)] containing electron-push-pull groups have been prepared. They present a planar N-benzylideneaniline core and neighbouring functional atoms, which are related through an efficient intramolecular charge transfer (CT). Two of the derivatives crystallize in non-centrosymmetric space groups, a necessary condition for non-linear optical (NLO) responses. The NLO properties were calculated for the molecular conformations determined by single-crystal X-ray diffraction as well as for the four molecules packed into each corresponding unit cell, using a quantum-chemical method at the cam-B3LYP/NLO-V level of theory. As expected from antiparallel face-to-face stacking through centrosymmetry, the main NLO descriptors - namely, the first hyperpolarizability (βtot) and its projection on the dipole moment direction (βvec) - are almost zero for the tetramer of derivative III. Interestingly, the calculated first hyperpolarizability decreases in the non-centrosymmetric unit-cell content of derivative II when compared to its single molecule, which may be related to its molecular pillaring, similar to that observed in derivative III. On the other hand, a desirable magnification of the NLO properties was found for packed units of derivative I, which may be a consequence of its parallel face-to-tail stacking with the CT vectors of all molecules pointing in the same direction. Moreover, the CT vector of compound I makes an angle of θ = 33.6° with its crystal polar axis, resulting in a higher-order parameter (cos(3)θ = 0.6) compared with the other derivatives. This is in line with the higher macroscopic second-order NLO response predicted for derivative I, βtot = 120.4 × 10(-30) e.s.u.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Influence of Synthetic Methods in the Structure and Dimensionality of Coordination Polymers

Eight different coordination polymers (CPs) of Co²⁺ and Zn²⁺ ions with rigid polycarboxylate ligands (fumaric acid (<i>fum</i>) and 2,5-dihydroxyterephalic acid (<i>dhbdc</i>)) have been synthesized using the same solvents, stoichiometry, and counterion but two different synthetic methods: liquid–liquid diffusion method–method A and pH control method–method B. The synthesis using method A resulted in four novel CPs: <i>trans</i>-Co­(dmso)₂­(H₂O)₂­(fum)]_<i>n</i> (<b>1</b>), [<i>trans</i>-Zn­(dmso)₂­(H₂O)₂­(fum)]_<i>n</i> (<b>2</b>), <i>trans</i>-Co­(dmso)₂­(H₂O)₂­(dhbdc)]_<i>n</i> (<b>3</b>), and [<i>trans</i>-Zn­(dmso)₂­(H₂O)₂­(dhbdc)]_<i>n</i> (<b>4</b>). Synthesis using method B resulted in one new ([Zn­(fum)­(OH)₂] (<b>6</b>)) and three previously described CPs ([Co₃(H₂O)₄­(OH)₂­(fum)₂]­·2H₂O (<b>5</b>), [Co₂(dobdc)] (<b>7</b>), and [Zn₂(dobdc)] (<b>8</b>), where <i>dobdc</i> = 2,5-dioxyterephtalic acid). The new CPs (<b>1</b>–<b>4</b>) were also structurally investigated by single-crystal X-ray diffraction techniques, which showed that all of them form one-dimensional (1D) CPs with linear chain structure: it was evidenced that (<b>1</b>) and (<b>3</b>) are isomorphus crystals of (<b>2</b>) and (<b>4</b>), respectively. The crystal structures of <b>1</b>–<b>4</b> were compared with similar 1D, two- and three-dimensional (2D and 3D) CPs reported in the literature. Intra- and interchain H-bond networks and coordination (<i>fum</i>, <i>dhbdc</i>, DMSO, water) as well as linkage (<i>fum</i> and <i>dhbdc</i>) isomerism guide the chain configuration (linear or zigzag). It was also demonstrated that the new series of 1D CPs synthesized here (<b>1</b>–<b>4</b>) can work as precursors for CP with higher dimensionality. Our studies showed that the synthetic method plays a crucial role in the crystal growth of coordination polymers