Non-inclusion complexes between riboflavin and cyclodextrins

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

THE EFFECT of ANIONIC SORPTION on THE METAKAOLINITE

This paper reports an investigation on the effect of thermal activation of kaolinite. It is well known that during calcinations (400-650 degrees C), kaolinite loses the OH lattice water and is transformed into metakaolinite or amorphous material. Arsenic is trace element that is toxic to animals including humans. The adsorption of arsenic on kaolinite was investigated at varying pH and thermal pretreatment. Calcination of sample is carried out at 650 degrees C for 3 h. The decomposition of kaolinite is recorded using methods of thermal analysis. The resultant product is identified by XRD. Laboratory experiments were conducted examining the effect of arsenic by thermally modified kaolinite. The Langmuir isotherm was used to describe arsenite and arsenate sorption by the calcined kaolinite. The equilibrium parameters used were based on experimental data obtained for the dynamic adsorption process of arsenic. Removal of arsenate using natural kaolinite was satisfactory, whereas arsenic was not removed by adsorption with thermally modified kaolinite. Moreover, the adsorption of arsenic by kaolinite and metakaolinite decreases with increasing pH.

Improvement of the oral praziquantel anthelmintic effect by cyclodextrin complexation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Host-guest system of 4-nerolidylcatechol in 2-hydroxypropyl-beta-cyclodextrin: preparation, characterization and molecular modeling

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Nanotechnological delivery systems for the oral administration of active molecules: Polymeric microparticles and microemulsions applied to anti-inflammatory and anti-infectious drugs

This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit® S- 100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spraydried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on mediumchain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophiliclipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 μg/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB

Obtenção de sistemas multiparticulados de isoniazida revestidos com polímero de liberação entérica

Known for thousands of years, tuberculosis (TB) is the leading cause of mortality by a single infectious disease due to lack of patient adherence to available treatment regimens, the rising of multidrug resistant strains of TB (MDR-TB) and co-infection with HIV virus. Isoniazid and rifampicin are the most powerful bactericidal agents against M. tuberculosis. Because of that, this couple of drugs becomes unanimity in anti-TB treatment around the world. However, the rifampicin in acidic conditions in the stomach can be degraded rapidly, especially in the presence of isoniazid, which reduces the amount of available drug for absorption, as well as its bioavailability, contributing to the growing resistance to tuberculostatic drugs. Rifampicin is well absorbed in the stomach because of its high solubility between pH 1 and 2 and the gastric absorption of isoniazid is considered poor, therefore it is mostly intestinal. This work has as objective the development of gastro-resistant multiple-systems (granules and pellets) of isoniazid aiming to prevent the contact with rifampicin, with consequent degradation in acid stomach and modulate the release of isoniazid in the intestine. Granules of isoniazid were obtained by wet method using both alcoholic and aqueous solutions of PVP K-30 as aggregating and binder agent, at proportions of 5, 8 and 10%. The influence of the excipients (starch, cellulose or filler default) on the physical and technological properties of the granules was investigated. The pellets were produced by extrusionesferonization technique using isoniazid and microcrystalline cellulose MC 101 (at the proportion of 85:15) and aqueous solution of 1% Methocel as platelet. The pellets presented advantages over granular, such as: higher apparent density, smaller difference between apparent and compaction densities, smoother surface and, especially, smaller friability, and then were coated with an organic solution of Acrycoat L 100 ® in a fluidized bed. Different percentages of coating (15, 25 and 50%) were applied to the pellets which had their behavior evaluated in vitro by dissolution in acidic and basic medium. Rifampicin dissolution in the presence of uncoated and coated isoniazid pellets was evaluated too. The results indicate that the gastro resistance was only achieved with the greatest amount of coating and isoniazid is released successfully in basic step. The amount of rifampicin in the dissolution medium when the isoniazid pellets were not coated was lower than in the presence of enteric release pellets. Therefore, the polymer Acrycoat L 100 ® was efficient for coating with gastro-resistant function and can solve the problem of low bioavailability of rifampicin and help to reduce its dosage

Changes in physical properties of extruded sour cassava starch and quinoa flour blend snacks

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Produção de snacks funcionais à base de farinha de soja e polvilho azedo

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Preparação e carcterização de complexos multicomponentes contendo ciclodextrinas e benznidazol

The benznidazole (BNZ) is the only alternative for Chagas disease treatment in Brazil. This drug has low solubility, which restricts its dissolution rate. Thus, the present work aimed to study the BNZ interactions in binary systems with beta cyclodextrin (β-CD) and hydroxypropyl-beta cyclodextrin (HP-β-CD), in order to increase the apparent aqueous solubility of drug. The influence of seven hydrophilic polymers, triethanolamine (TEA) and 1-methyl-2- pyrrolidone (NMP) in benznidazole apparent aqueous solubility, as well as the formation of inclusion complexes was also investigated. The interactions in solution were predicted and investigated using phase solubility diagram methodology, nuclear magnetic resonance of protons (RMN) and molecular modeling. Complexes were obtained in solid phase by spray drying and physicochemical characterization included the UV-Vis spectrophotometric spectroscopy in the infrared region, scanning electron microscopy, X-ray diffraction and dissolution drug test from the different systems. The increment on apparent aqueous solubility of drug was achieved with a linear type (AL) in presence of both cyclodextrins at different pH values. The hydrophilic polymers and 1-methyl-2-pyrrolidone contributes to the formation of inclusion complexes, while the triethanolamine decreased the complex stability constant (Kc). The log-linear model applied for solubility diagrams revealed that both triethanolamine and 1-methyl-2-pyrrolidone showed an action cosolvent (both solvents) and complexing (1-methyl-2-pyrrolidone). The best results were obtained with complexes involving 1-methyl-2-pyrrolidone and hydroxypropylbeta- cyclodextrin, with an increased of benznidazole solubility in 27.9 and 9.4 times, respectively. The complexes effectiveness was proven by dissolution tests, in which the ternary complexes and physical mixtures involving 1-methyl- 2-pyrrolidone and both cyclodextrins investigated showed better results, showing the potential use as novel pharmaceutical ingredient, that leads to increased benznidazole bioavailability

Preparação e caracterização de sistemas emulsionados lipidicos contendo praziquantel

Praziquantel (PRZ) is the main drug used for treatment of schistosomiasis in Brazil. It is administered by oral rout as tablets. However, has low aqueous solubility which limits this therapeutic success dosage form and availability of liquid forms. The emulsion systems have great potential and represent an interesting strategy to increase the solubility of drugs. The aim of study was the development and characterization of lipid-emulsified liquid systems of the type oil in water (O / W), the base of soybean oil as the internal phase stabilized by surfactants pair Tween® 80 and Span® 80, for improving the phase biopharmaceutical of PRZ. After selecting the best value of Hydrophilic-Lipophilic Balance (HLB = 11), the parameters of the preparation of the formulations were optimized emulsification technique. The emulsions were successfully obtained; the liquid forms provided exhibited Newtonian behavior and an increase in solubility of PRZ higher than 20 times. The accelerated stability study demonstrated the stability of the emulsions and the effect of cosurfactants investigated. The study of the dynamics of interaction between components in the diagram showed pseudoternary phase regions to obtain O/W emulsions, whereas the study of the interaction of the components and their effect on system structure and the efficiency of incorporation of the drug led to systems with an amount of soluble drug even higher (about 1.5%), which demonstrates the potential of this new input mainly for the treatment of schistosomiasis, which resulted in the filing of patent BR 10 2013 0004 55 3

Dispersões sólidas de sinvastatina: preparação, caracterização, no estado sólido utilizando técnicas emergentes e estudo de estabilidade

This thesis aimed to assess the increase in solubility of simvastatin (SINV) with solid dispersions using techniques such as kneading (MA), co-solvent evaporation (ES), melting carrier (FC) and spray dryer (SD). Soluplus (SOL), PEG 6000 (PEG), PVP K-30 (PVP) e sodium lauryl sulphate (LSS) were used as carriers. The solid dispersions containing PEG [PEG-2(SD)], Soluplus [SOL-2(MA)] and sodium lauryl sulphate [LSS-2(ES)] were presented with a greater increase in solubility (5.02, 5.60 and 5.43 times respectively); analyses by ANOVA between the three groups did not present significant difference (p<0.05). In the phase solubility study, the calculation of the Gibbs free energy (ΔG) revealed that the spontaneity of solubilisation of SINV occurred in the order SOL>PEG >PVP 75%>LSS, always 80%. The phase diagrams of PEG and LSS presented solubilization stoichiometry of type 1:1 (type AL). The diagrams with PVP and SOL tend to 1:2 stoichiometry (type AL + AP). The stability coefficients (Ks) of the phase diagrams revealed that the most stable reactions occurred with LSS and PVP. The solid dispersions were characterized by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), particle size distribution (PSD), near-infrared spectroscopy imaging (NIR-CI) and X-ray diffraction of the powder using the Topas software (PDRX-TOPAS). The solid dispersion PEG-2(SD) presented the greatest homogeneity and the lowest degree of crystallinity (18.2%). The accelerated stability study revealed that the solid dispersions are less stable than SINV, with PEG-2(SD) being the least stable, confirmed by FTIR and DSC. The analyses by PDRX-TOPAS revealed the amorphous character of the dispersions and the mechanism of increasing solubility

Effects of hypercapnic hyperpnea on recovery from isoflurane or sevoflurane anesthesia in horses

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Métodos para estudo das respostas metabólicas de cães e gatos a diferentes alimentos

Durante o processo de assimilação e uso dos alimentos, diferentes respostas metabólicas podem ser desenvolvidas pelo organismo dos animais. Estas respostas são fruto da integração de mecanismos complexos, que envolvem os sistemas neuro-endócrino e o funcionamento dos órgãos, sendo influenciadas pela dieta, espécie animal, idade, condição fisiológica e composição corporal. Este trabalho enfoca a importância fisiológica e os métodos de estudo das respostas pós-prandiais aos carboidratos, bem como as alterações fisiológicas conseqüentes ao balanço eletrolítico da dieta. A quantidade, estrutura química e processamento industrial do amido determinam boa parte da resposta pós-prandial de glicose e insulina de cães. em gatos, outros mecanismos parecem ser mais importantes, como a ingestão de aminoácidos. A fibra alimentar também altera a resposta pós-prandial ao alimento, devendo ser consideradas sua quantidade, solubilidade e fermentabilidade no desenvolvimento das dietas. Os métodos de estudo destas respostas incluem avaliação das respostas glicêmica e insulínca pós-prandiais, teste endovenoso de tolerância à glicose e à arginina. O clâmp euglicêmico apresenta-se também como ferramenta de estudo, no entanto revela informações mais relacionadas ao animal do que à dieta. A compreensão do conjunto de alterações metabólicas aos carboidratos é importante no estudo do controle da saciedade, composição corporal e inúmeras doenças degenerativas e endócrinas. A concentração e relação entre os macro-elementos da dieta (Na, Cl, K, P, Ca, Mg e S) e dos aminoácidos sulfurados (metionina, cistina e taurina) interferem em inúmeras funções orgânicas, como a cardiovascular, neuromuscular, metabolismo ósseo, renal e pulmonar, refletindo-se no equilíbrio hidro-eletrolítico e ácido-básico orgânicos. de importância prática para cães e gatos encontram-se a relação destes nutrientes com cardiopatias, nefropatias, osteodistrofias e urolitíases. A relação entre os macro-elementos é estabelecida em mmol/kg de matéria seca da dieta, calculando-se seu balanço cátion-ânion (excesso de bases ou ânions dietéticos não determinados). Suas repostas orgânicas são medidas, dentre outros métodos, pela hemogasimetria, balanço hídrico, mensuração do volume dos espaços extracelular e vascular, supersaturação e pH urinários.

The status of soil phosphate fractions and the ability of fungi to dissolve hardly soluble phosphates

Brazilian soils predominantly consist of iron and aluminum oxides and have a low phosphorus content. The present study was carried out in order to assess the status of phosphate fractions in pasture, forest and agricultural soils and the ability of soil fungi to solubilize iron and aluminum phosphates. The abundance of P fractions in the soils studied occurred in the following order: Fe-P > reductant-soluble Fe-P > occluded Fe-P > occluded Al-P > Al-P > Ca-P. of the 481 fungi isolated, 33 showed the ability to solubilize the inorganic phosphates in culture. of these, 14 were considered to be high or very high solubilizers based on a solubilization capacity > 1000 mu g PO43- ml(-1). Isolate F-111 was the only one that dissolved all the insoluble phosphates used. Nine isolates solubilized both Al-P and Ca-P, and four other isolates only solubilized Ca-P. The highest number of isolates with high solubilization capacity were detected in pasture soil, followed by tropical rain forest and forest patch soils. Pasture soil presented both the largest contents of insoluble phosphates and the largest number of fungal isolates with phosphate-solubilizing ability. The range and size of P fractions influenced the number of fungi and their ability to solubilize hardly soluble phosphates. (c) 2004 Elsevier B.V. All rights reserved.

Solubilidade de calcários em extratores químicos

A solubilidade de quatro calcários agrícolas, dois sedimentares e dois metamórficos, divididos em quatro frações granulométricas, foi estudada em dois extratores químicos (soluções de ácido clorídrico e de ácido acético), em variadas condições, com o objetivo de avaliar a eficiência desses materiais através desse critério. Os resultados obtidos, comparados com os ensaios de incubação com solos, mostraram que para a pretendida avaliação, os extratores não se prestam para avaliar os calcários agrícolas, visto que não há correlação entre a solubilidade, expressa em equivalente de CaCO3, e a eficiência mostrada nos ensaios de incubação com solos.