Caracterização do estado sólido de ganciclovir / Solid state characterization of ganciclovir

O presente trabalho teve como objetivo o estudo do estado sólido do ganciclovir (GCV) e suas diferentes formas polimórficas. O GCV é um fármaco antiviral útil no tratamento de infecções por citomegalovírus (CMV). Embora seja um fármaco amplamente usado, poucos estudos têm sido realizados sobre seu estado sólido. Atualmente, o GCV é conhecido por apresentar quatro formas cristalinas, duas anidras (Forma I e II) e duas hidratas (III e IV). Neste trabalho, nós reportamos a solução da estrutura cristalográfica da Forma I do GCV, que foi encontrado durante o screening de cristalização do fármaco, em que nove ensaios de cristalização (GCV-1, GCV-A, GCV-B, GCV-C, GCV-D, GCV-E, GCV-F, GCV-G e GCV-H) foram realizados e os materiais resultantes foram caracterizados por Difratometria de raios X (DRX), análise térmica (DTA/TG) e Hot Stage Microscopy. De todas as cristalizações realizadas foram obtidas quatro formas sólidas, denominadas como Forma I (GCV-1, GCV-B e GCV-H), Forma III (GCV-C, GCV-D, GCV-F e GCV-G), Forma IV (GCV-A) e Forma V (GCV-E). Esta última está sendo descrita pela primeira vez na literatura e indica a presença de outra forma hidratada de GCV. As Formas I, III e IV corresponderam a forma anidra e as duas formas hidratadas do fármaco, respectivamente. Além disso, foi evidenciado por experimentos de conversão de slurry e análise térmica que o cristalizado de GCV-1 (Forma I) foi o mais estável entre os materiais obtidos, e este deu origem ao monocristal da Forma I de GCV, estrutura cristalina anidra do fármaco. Neste trabalho, pela primeira vez, a estrutura cristalina deste composto foi definida por cristalografia de raios X de monocristal. A análise estrutural mostrou que a Forma I do fármaco cristaliza no grupo espacial monoclínico P21/c e está composta por quatro moléculas de GCV na sua unidade assimétrica. Cada molécula está unida intermolecularmente por ligações de hidrogênio, que dão lugar à formação de cadeias infinitas e estas por sua vez se arranjam de maneira a formar uma estrutura tridimensional.

This presented work aims to study the solid state of ganciclovir (GCV) and its different polymorphic forms. GCV is an antiviral drug useful in the treatment of cytomegalovirus (CMV) infections. Although it is a widely-used drug, few studies have been conducted on its solid state. Currently, GCV is known to have four crystalline forms, two anhydrous (Form I and II) and two hydrates (III and IV). In this investigation, we report a successful preparation of GCV Form I and its crystallographic structure, which was found during the crystallization of the drug, in which nine crystallization tests (GCV-1, GCV-A, GCV-B, GCV- D, GCV-E, GCV-F, GCV-G and GCV-H) were performed and the resulting materials were characterized by X-ray diffractometry (XRD), thermal analysis (DTA/TG) and Hot Stage Microscopy. Of all the crystallizations performed, four solid forms were obtained, denoted as Form I (GCV-1, GCV-B and GCV- H), Form III (GCV-C, GCV-D, GCV-F and GCV-G), Form IV (GCV-A) and Form V (GCV-E). The latter is being described for the first time in the literature and indicates the presence of another hydrated form of GCV. Forms I, III and IV corresponded to the anhydrous form and the two hydrated forms of the drug, respectively. In addition, it was evident by both the slurry conversion and the thermal analysis methods that the GCV-1 crystallized (Form I) was indeed the most stable amongst the materials obtained. This gave rise to GCV Form I monocrystal, anhydrous crystalline structure of the drug. The compound was characterized by monocrystal X-ray crystallography. The structural analysis showed that Form I of the drug crystallized in the monoclinic system space group P21/c is composed of four molecules of GCV in its asymmetric unit. Each molecule is linked intermolecularly by hydrogen bonds, which give rise to the formation of infinite chains arranged in a way that form a three-dimensional structure.

Estudo de propriedades físico-químicas de metalofármacos de dirutênio com anti-inflamatórios não esteroides / Study of physico-chemical properties of diruthenium metallodrugs with non-steroidal anti-inflammatory drugs

Complexos de rutênio, em razão da menor toxicidade e por poderem exibir atividade citotóxica ou antimetastática, tem sido considerados como alternativas potencialmente promissoras aos complexos de platina para tratamento de câncer. Nosso grupo de pesquisa tem investigado a interação de íons metálicos com fármacos anti-inflamatórios não esteroides (FAINEs) e já obteve sucesso na preparação de metalofármacos de dirutênio(II,III)-FAINEs, os quais se mostraram promissores com relação à atividade frente a modelos de glioma. Com a finalidade de contribuir para o entendimento das propriedades físico-químicas desses complexos, o presente trabalho teve como principal objetivo analisar propriedades consideradas particularmente essenciais a um potencial candidato a fármaco, tais como, estabilidade no estado sólido, lipofilicidade, solubilidade aquosa e dissolução intrínseca. Um complexo inédito de fórmula [Ru2Cl(feno)4], em que feno = fenoprofenato, foi sintetizado e caracterizado por meio de análise elementar, espectroscopia eletrônica, espectroscopia vibracional, difratometria de raios X, análise térmica e espectrometria de massas. Os complexos já testados anteriormente para atividade biológica, [Ru2Cl(ibp)4], ibp = ibuprofenato, e [Ru2(cet)4Cl], cet = cetoprofenato, foram analisados quanto à estabilidade no estado sólido por meio da determinação isotérmica de variação de massa. As lipofilicidades desses dois complexos, juntamente com a dos fármacos de origem e a do precursor sintético [Ru2(O2CH3)4Cl], foram avaliadas pelo método shake flask, e suas solubilidade aquosas foram investigadas em presença de co-solventes alcoólicos. Investigou-se ainda a velocidade de dissolução intrínseca do [Ru2Cl(ibp)4] que se encontra em estágio avançado de estudos biológicos. Os resultados obtidos trazem novas informações sobre o comportamento térmico dos complexos e sobre suas características biofarmacêutica

Ruthenium complexes, mainly due to the lower toxicity and the cytotoxic and anti-metastatic activities, have been considered as potentially promising alternatives to platinum drugs for cancer treatment. Our research group has investigated the interactions of diruthenium metal cores with anti-inflammatory non-steroidal drugs (NSAIDs) and succeeded in preparing diruthenium(II,III)-NSAIDs metallodrugs which show promising activity against glioma models. With the aim of elucidating the physico-chemical properties of these complexes, the major objective of the present work was to investigate properties which are considered as essential for a potential candidate to drug, e.g., stability in the solid state, lipophilicity, aqueous solubility and intrinsic dissolution. A new complex of formula [Ru2Cl(feno)4], where feno = fenoprofen, was synthesized and characterized by elemental analysis, electronic spectroscopy, vibrational spectroscopy, X-rays difractommetry, thermal analysis and mass spectrometry. The complexes previously tested for biological properties, [Ru2Cl(ibp)4], ibp = ibuprofenate, and [Ru2(cet)4Cl], cet = cetoprofenate, were inv estigated for the stability in the solid state by isothermal thermogravimetry. The lipophilicity of the se complexes, as well as those of the parent drugs and of the precursor [Ru2(O2CH3)4Cl], was evaluated by the shake flask method, and their aqueous solubility in the presence of alcohol co-solvents was investigated. In addition, the intrinsic dissolution rate was determined for [Ru2Cl(ibp)4], which is undergoing advanced biological studies. The results provide important new information on the thermal behavior of the complexes and also on their biopharmaceutical propertie

thermal analysis study of the tenoxicam

This study focuses on the decomposition of tenoxicam alone. The raw material's purity, kinetic parameters, thermal behavior and melting characteristics were determined by differential scanning calorimetry and thermogravimetric analysis. TG.DTA and DSC unit using in an inert atmosphere of flowing nitrogen. The compound was subject to temperature ramp after heating rates, 5, 10, 15, 20, 25 from ambient to 800 C. Mass spectrometry was used as adjunctary technique to identify the products of the decomposition reaction. It was observed that tenoxicam decomposed via multistage reaction following melting. The purity was 99.01 +/- 0.16. The thermal decomposition followed first order kinetic, activation energy 87.31 kJ mol and frequency factor of 3.941.I0[7] min[-1]

Synthesis, spectroscopic characterization, thermal investigation and antimicrobial activity of S, O and N-donor heterocyclic schiff base ligands and their Co[II], Cd[II], Hg[II], Fe[III] and UO[2][II] metal complexes

The polydentate ligands 2,5-N,N-bis [dimethy1-1-pheny1-4-pyrazoline-5-one] furanidine; 2,5-N,N-bis [pyridine]furanidine and 2,5-N, N-bis [2-thiophenol] furanidine [L[1]- L[3]], have been prepared and identified. The chemical behavior of these ligands towards some metal cations such as Co[II],Cd [II], Hg [II], Fe [III] and UO[2] [II] was studied. The isolated complexes are characterized using analytical data, IR, [1]H-NMR, UV-visible, mass spectroscopy, magnetic susceptibility, thermal analysis and molar conductance measurements. Bonding of the ligands with the metal ions is deducted from IR spectra and the presence of the mononuclear complexes are inferred from the mass spectral study. An octahedral structure is proposed for the prepared metal complexes and some ligand field parameters [D[q], B, and beta] in addition to LFSE were calculated from electronic spectral data. All synthesized compounds were screened for their antimicrobial activity against gram positive and gram negative bacteria and fungi. The biological evaluation study showed high to moderate bacterial activity compared with the ligands, their metal complexes and known antibiotics data

Estudo de metodologia analítica para a determinação do cetoconazol em formulações farmacêuticas / Study of analytical methodology for ketoconazole determination in pharmaceutical preparation

Cetoconazol é um antifúngico sintético, derivado imidazólico de amplo espectro de ação, efetivo no tratamento de infecções superficiais e sistêmicas. Foram estudadas diferentes metodologias para análise do cetoconazol em especialidades farmacêuticas diversas usando espectrofotometria no ultravioleta, no infravermelho e análise térmica. Os resultados mostram que a espectrofotometria ultravioleta é um método rápido, prático e econômico e apontam que outros métodos como a espectrofotometria no infravermelho e análise térmica são uma alternativa à análise do cetoconazol em diferentes especialidades farmacêuticas.

Ketoconazole is a synthetic broad-spectrum oral and topical antifungal drug derived from imidazole, effective in the treatment of superficial mycoses and systemic infections. In this study we have tested several methods to analyze ketoconazole in various pharmaceutical products containing this drug, employing techniques such as UV and IR spectrophotometry and thermal analysis. The results showed that UV spectrophotometryis a fast, practical and economical method and indicated that other methods, such as IR spectrophotometry and thermal analysis, could be good alternative methods for ketoconazole analysis in certain pharmaceutical forms.

Spectrometric, thermal and electron microscope studies of iron complexes of adrenaline hydrogen tartrate and catecholamine

Iron was found to form coloured stable complexes with both adrenaline hydrogen tartrate and catechol as inhibitors for iron corrosion in aqueous solutions of different pH values [2.0-11.5]. The electrochemically formed complexes on the surface of the iron electrode in different media were separated and studied in comparison with the same complexes prepared by chemical method in the same media. The prepared complexes were studied using micro-, electro-and thermal analyses together with electron ionization mass [EI-MS] and IR spectral methods. Both chemically and electrochemically prepared complexes were found to be of the same structures. The electrochemically formed complex in different media was found to be as a chemisorbed layer on the surface of iron electrode. The aim of the present work is to compare the results of chemical and electrochemical techniques in preparation of stable iron chelates of both adrenaline hydrogen tatrate [AHT] and Catechol [Cat.] as inhibitors for iron corrosion. The morphology of the chemisorbed complex layers on the electrode surface was also tested by electron microscope [EMS] and characterized as an amorphous or crystalline adsorbents

Investigation of molecula structure - chirality relationship of ephedrine and pseudoephedrine drug using thermal analyses and mass spectrometry techniques combined with MO-calculations

Two diastercoisomers ephedra drugs namely; ephedrine [eph.] and pseudoephedrine [psi-eph.] hydrochloride, have been investigated for their chirality using thermal analysis [TA] measurement [TG/DTA] and electron ionization mass spectrometry [EI-MS] at 70 eV. Monte Carlo conformational search technique was used for exploration of conformational space of ephedrine and psi-eph., using Amber force field molecular mechanics method. MO-calculations were performed using semi-empirical PM3 procedure on the obtained conformational sample for investigation of the different molecular properties. The calculations include bond length, bond order, charge distribution, ionization energy and heat of formation, in neutral and positively charged forms for the two drugs. The effect of diastereoisomerism on thermal analysis decomposition behavior of these drugs was studied. The obtained data confirmed the chirality and declared the structure reactivity relationship of these drugs

Sol-gel synthesis of nanosized titanium phosphates

Alpha-titanium phosphate was prepared by three methods: Solid-solid reaction, Direct precipitation and Sol-gel methods. The produced samples were dried and characterized by using X-ray diffraction, IR spectra, thermal analysis and scanning electron microscopy. For the samples prepared by solid-solid reaction, a residual of unreacted materials was observed which disappeared by increasing the sintering temperature. The other two methods give a crystalline single phase of alpha-TiP. By increasing the refluxing time, the crystallinity of the samples improved. The IR results show the main absorption bands which characterized the phosphate compounds. Also, the IR patterns indicate that the TiP is coordinated as Ti-O-P-O-Ti and not TiO2 which coordinated as Ti-O-Ti. The thermal analysis indicates that the alpha-TiP underwent dehydration and it converted to alpha-TiP2O7 at high temperature. The characterization of the different samples indicates that the products depend on the method of preparation and on the controlled preparation

Enhancement of dissolution properties of repaglinide using liquisolid compacts

The potential of liquisolid systems to improve the dissolution properties of water insoluble drugs was investigated using repaglinide as the model medication. The new formulation technique of liquisolid compacts was used to convert liquid medications such as solution or suspension of repaglinide in polysorbate 80, a non-volatile liquid vehicle, into acceptably flowing and compressible powders by blending with selective powder excipients. Several liquisolid tablet formulations were prepared using a new mathematical model to calculate the appropriate quantities of powder and liquid ingredients required to produce acceptably flowing and compressible admixtures. Due to their increased wetting properties and surface of drug available for dissolution. liquisolid compacts demonstrated significantly higher drug release rate than that of commercial products. Differential thermal analysis [DTA] was used for evaluation of physicochemical properties of repaglinide in liquisolid formula. It was shown that Avicel PH101 had more liquid retention potential in comparison with starch, and the formulations containing polysorbate 80 as a liquid medication, Avicel PH101 as a carrier and calcium silicate as a coat. showed higher dissolution rate at excipients ratio 5

Transition metal complexes with pyrazolone based ligand. thermogravimetric and spectroscopic studies

Transition metal complexes of Schiff base ligand [L] derived I from thiophene 2-carboxaldehyde and 4-aminoantipyrine have been synthesized to study possible structural determination for these complexes using spectroscopic and conductivity methods. Magnetic susceptibility measurements and thermal analysis were performed. Elemental analysis and conductometric titration showed the stoichiometry of the complexes. The molar conductivities of the complexes indicate that all complexes are non-electrolyte, except Ni[2+] complex behaves as 1:2 electrolyte and Zn[2+] complex is 1:1 electrolyte. Magnetic susceptibility measurements and electronic absorption spectra suggest tetrahedral geometry for CO[+2] chelate, The diamagnetic behaviour of Ni[2+] chelate indicates a square planer configuration, distorted octahedral structure for Cu[2+] chelate, Hg[2+] and Fe[3+] chelates have octahedral configuration and Zn[2+] chelate has square planar structure. Thermal studies indicate weight loss associated with water molecules. Some of the complexes show antibacterial and antifungal activities against four species of bacteria as well as four species of fungi and the results were compared with known antibiotics

Avaliaçäo frente a ensaio de torçäo de diferentes limas endodônticas submetidas ou näo a um tratamento térmico recristalizador / Evaluation through torsional test of different endodontic files submitted or not to a thermal treatment

Determinou-se um tipo de tratamento térmico recristalizador que pudesse melhorar algumas propriedades mecânicas dos instrumentos, na inteçäo de se obter um produto de utilizaçäo mais segura. Tal tratamento foi empregado em limas tipo K, marcas Kerr e Maillefer, e em limas Flexofile e Trifile, de números 15, 25 e 35. Como critério para avaliaçäo da efetividade da recristalizaçäo, foi empregado o ensaio de resistência à torçäo, medida em graus. Os resultados mostraram que a temperatura de 600ºC por uma hora foi capaz de proporcionar um aumento substancial na resistência à torçäo dos instrumentos estudados, da ordem de 30 a 102 por cento

Adesividade do cimento de ionômero de vidro à dentina e ligas odontológicas / Adhesivity of the ionomer cements to dentin and dental alloys

Foi estudada a retentividade do cimento de ionômero de vidro à dentina e ligas metálicas. Corpos de prova de dentina e ligas foram cimentadas entre si e submetidos a ensaios de traçäo. Para a dentina empregou-se um cimento Vitrion C e dois para os metais. Estes tiveram superficies rugosas e lisas. Os ensaios foram feitos após um dia de imersäo e após 25 dias com alternância de ciclagem térmica. Os resultados permitiram concluir que: a retençäo à dentina é baixa, mas näo sofre diminuiçäo com imersäo prolongada; a liga de niquel-cromo é mais retentiva que a do cobre-alumínio; o cimento Ketac-Cem é mais retentivo que o Vidrion C; a superficie rugosa propicia maior retentividade; a superfície lisa com imersäo prolongada e ciclagem térmica quase sempre termina em retençäo nula

Reacción de los ionómeros de vidrio tipo II a las pruebas de termociclaje / Reaction of type II glass ionomer cements to the thermocycling test

En este artículo se describe un estudio realizado para evaluar "in vitro" la reacción de los ionómeros de vidrio a las pruebas de termociclaje, utilizando 60 dientes, cada uno con cuatro cavidades clase V, que se obturaron con ionómeros de vidrio tipo II de tres casas comerciales diferentes (Fuji, Chemfill, Ketac) solos, con resina líquida, imprimador o ácido maleico. Después de evaluar el estudio se demostró que existe una menor filtración marginal cuando se utiliza el ionómero de vidrio tipo II Fuji, sin ningún medio de unión