Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-06-02T21:45:30Z No. of bitstreams: 1 IzadoraDeSouza_DISSERT.pdf: 2477888 bytes, checksum: 7568590836d5bc820ccba775908ac117 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-06-07T19:21:19Z (GMT) No. of bitstreams: 1 IzadoraDeSouza_DISSERT.pdf: 2477888 bytes, checksum: 7568590836d5bc820ccba775908ac117 (MD5) / Made available in DSpace on 2017-06-07T19:21:19Z (GMT). No. of bitstreams: 1 IzadoraDeSouza_DISSERT.pdf: 2477888 bytes, checksum: 7568590836d5bc820ccba775908ac117 (MD5) Previous issue date: 2015-07-31 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Cristais l?quidos (CL) possuem um arranjo molecular bastante estruturado que combina propriedades dos estados l?quido e s?lido, bem como o fluxo dos l?quidos e a ordena??o da estrutura cristalina dos s?lidos. Foram testadas t?cnicas de alta e baixa energia para produzir CL, utilizando oleato de s?dio, fosfatidilcolina de soja, ?leo de soja, N-metilpirrolidona (NMP) e ?gua. As intera??es entre NMP e oleato de s?dio da formula??o foram investigadas. CL obtidos por t?cnica de alta energia foram caracterizados por microscopia de luz polarizada (MLP), reologia e tamanho de part?cula. MLP exibiu estruturas que sugerem presen?a de CL lamelares. Na reologia, as amostras apresentaram viscosidade newtoniana limitante nas curvas de fluxo e uma diminui??o no grau de estrutura??o nos testes oscilat?rios, quando a concentra??o de NMP diminu?a. Uma nova t?cnica para obter sistemas lip?dicos de libera??o de f?rmacos foi desenvolvida a partir da dilui??o de CL produzidos por baixa energia. CL foram produzidos por agita??o magn?tica e, posteriormente, foram dilu?dos com ?gua e solu??o aquosa de NMP 10%, a 25 ? C e 70 ?C, em que foram avaliados tamanho de got?cula e incorpora??o de praziquantel (PRZ). Os sistemas dilu?dos com ?gua apresentaram menor faixa de tamanho (165,22 ? 381,26 nm) e maior faixa de incorpora??o de PRZ (40,96 ? 43,44 mg/mL) quando comparadas com as dilu?das com a solu??o de NMP. N?o houve contribui??o da solu??o de NMP para a forma??o de got?culas menores e para a maior incorpora??o de PRZ. Houve um aumento na solubilidade do PRZ em sistemas dilu?dos com ?gua, aumentando a fra??o sol?vel de f?rmaco em at? 200 vezes quando comparada ? sua solubilidade em ?gua. Testes utilizando Espalhamento de raios-X a baixo ?ngulo e MLP comprovaram a transi??o da mesofase lamelar para sistemas com micelas vermiformes, confirmando o sucesso da nova t?cnica em obter sistemas lip?dicos de libera??o de f?rmacos atrav?s da dilui??o de CL. / Liquid crystalline mesophase (LC) have an organized molecular arrangement and combining properties of liquid and solid state as the flow of liquids and the ordered and crystalline structure of solids. High- and low energy techniques were used to produce LC. N-methylpyrrolidone (NMP) and sodium oleate interactions with the system were investigated. LC fabricated by high-energy method were characterized by polarizing light microscopy (PLM), rheology and droplet size. PLM showed structures that indicated lamellar phases. Surface tension no important difference between the samples was observed. Rheology showed a zero shear viscosity in flow curves with a shear-thinning behavior in oscillatory tests, which with increasing of NMP, there was a decrease in degree of structure. Novel method to obtain lipid based drug delivery system (LBDDS) were developed through LC dilution and drug-loading was tested. LC fabricated with low-energy method was diluted with water and NMP 10% aqueous solution, at 25 ?C and 70 ?C, which droplet size and drug loading were evaluated. The systems diluted with water showed lower range size (165.22 nm- 381.26 nm) and higher drug-loading (40.96 mg/mL - 43.44 mg/mL) when compared with systems diluted by NMP solution. NMP aqueous solution did not contribute to form smaller particle size and higher praziquantel-loading. An increment in the apparent solubility of Praziquantel was achieved from incorporation in dilution of LC with water, increasing the soluble drug fraction approximately 200-fold when compared with water solubility. Small angle X-ray scattering (SAXS) measurements and PLM comproved the transition from lamellar mesophase to worm-like micelle systems confirming the success of new techinique for obtain LBDDS from LC dilution.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-06-02T21:45:30Z No. of bitstreams: 1 JairoSoteroNogueiraDeSouza_DISSERT.pdf: 2124011 bytes, checksum: 0d7ba6395004ada41813188b5d73116b (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-06-07T19:30:54Z (GMT) No. of bitstreams: 1 JairoSoteroNogueiraDeSouza_DISSERT.pdf: 2124011 bytes, checksum: 0d7ba6395004ada41813188b5d73116b (MD5) / Made available in DSpace on 2017-06-07T19:30:54Z (GMT). No. of bitstreams: 1 JairoSoteroNogueiraDeSouza_DISSERT.pdf: 2124011 bytes, checksum: 0d7ba6395004ada41813188b5d73116b (MD5) Previous issue date: 2016-11-28 / A utiliza??o de ciclodextrinas para aumentar a solubilidade de f?rmacos em solu??o aquosa tem sido bastante estudada. No presente estudo, o mecanismo de intera??o do praziquantel (PZQ) com a beta-ciclodextrina e com a hidroxipropil-beta-ciclodextrina na presen?a dos co-solventes trietanolamina (TEA) e a N-metilpirrolidona (NMP) foi realizado com o objetivo do aumento da solubilidade do praziquantel. Atrav?s dos diagramas de solubilidade e dos diagramas de Job?s Plot foi poss?vel observar a forma??o de complexos sol?veis com estequiometria 1:1. A presen?a dos co-solventes TEA e NMP diminuiu a estabilidade e solubilidade dos complexos formados, no entanto atrav?s dos estudos de modelagem molecular foi mostrado que este efeito pode facilitar a sa?da do f?rmaco da cavidade e, consequentemente, beneficiar a absor??o do f?rmaco. Os resultados mostraram-se elucidativos e bastantes promissores na obten??o futura de complexos que possam ser utilizados para melhor biodisponibilidade do praziquantel. / The use of cyclodextrin (CD) to enhace the praziquantel (PZQ) water solubility has been widely studied in the literature. In this present paper, the interaction has not yet studied between the PZQ and both the beta-cyclodextrin (?-CD) and hydroxyl-propyl-cyclodextrin (HP-?-CD) or its association with the solvents triethanolamine (TEA) and N-methyl-pyrrolidone (NMP) was carefully conducted with the purpose to enhance the water solubility of the PZQ. The solubility diagrams and job?s plot diagrams showed that water soluble complexes were formed with 1:1 stoichiometry. The association of the complexes with the TEA and NMP diminished considerably the complex stability and its solubility. However, throught the molecular modeling study it was showed that this effect may be beneficial for the output of the drug from the CD cavity, and consequently to benefit the drug absorption. The results showed up adequately enlightening to propose that these systems can be investigated to enhance the PZQ bioavailability.