Navegando por Palavras-chave "Ciclodextrinas"
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- ItemAcesso aberto (Open Access)Avaliação da permeabilidade da papaína em formulações orais para tratamento de patologias intestinais utilizando tripla co-cultura de células Caco-2, HT29-MTX e Raji como modelo in vitro(Universidade Federal de São Paulo, 2018-06-18) Corazza, Fulvio Gabriel [UNIFESP]; Lopes, Patricia Santos [UNIFESP]; Andréo Filho, Newton [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Papain is a phytoenzyme used in therapy for the treatment of wounds due to its proteolytic debridant activity capable of stimulating healing. Besides that, this enzyme can also be used as pharmaceutical actives permeation enhancer. The objective of the present study was to evaluate in vitro the cytotoxicity, phototoxicity, genotoxicity and capacity of samples containing free and complex papain with β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin and minitablets containing free papain in promoting the maintenance of furosemide through the Caco-2 cell monolayer and the triple co-culture of Caco-2, HT29-MTX and Raji cells. IC50 (μM) of papain on BALB/c 3T3 cells, CHO-K1, Caco-2, HuTu 80, HT-29, HT29-MTX, Raji. Hep G2 and human fibroblasts was 3.8; 4.9; 1.4; 0.4; 4,5; 2,3; 2.6 and 1.6, respectively. The IC50 (μM) of papain complexed with β-cyclodextrin on the same cell lines was 3.7; 3.5; 1.4; 2.8; 5.3; 1.9; 3.0; 1.8, respectively. The IC50 (μM) of papain complexed with 2-hydroxypropyl-β-cyclodextrin on the same cell lines was 4, 2; 2.5; 1,3; 3.3; 5.1; 1.8; 2.9; 1.5, respectively. Papain formulations did not show cytotoxicity on Raji cells and were unable to promote LDH release. In the phototoxicity evaluation, papain and its cyclodextrin complex were considered nonphototoxic at concentrations lower than 0.67 μM. In the genotoxicity assessment, the samples also did not promote genotoxicity on CHO-K1 and Hep G2 cells at the concentrations evaluated. Using the Caco-2 cell monolayer model, the Papp of furosemide was 2.8 x 10-6 cm.s1 and 7.0 x 10-6 cm.s-1 in the presence of the formulations of papain complexed with cyclodextrins. Meproprolol showed Papp of 24 x 10-6 cm.s-1 . rhodamine 123 (ROD123) efflux ratio was 0.2 and the Lucifer Yellow (LY) Papp was 4.3 x 10-7 cm.s-1 , indicating the presence of P-gp and paracellular integrity. Using the triple co-culture monolayer model, Papp of furosemide was 0.6 x 10-6 cm.s-1 and on average 0.8 x 10-6 cm.s-1 in the presence of formulations of papain complexed with cyclodextrins. Meproprolol presented Papp of 7.1 x 10-6 cm.s-1 . The ROD123 efflux ratio was 0.1 and the LY Papp was 3.8 x 10-7 cm.s-1 , indicating the presence of P-gp and maintaining the paracellular integrity of the cell monolayer. The results presented suggest that papain formulations complexed with cyclodextrins could be employed not only as therapeutic agents in the treatment of colonic pathologies but also as therapeutic adjuvants foccus in promoting permeation of drugs which have low oral permeability.
- ItemSomente MetadadadosDesenvolvimento de minicomprimidos veiculando papaína livre e complexada com ciclodextrinas para a liberação imediata.(Universidade Federal de São Paulo, 2018-08-23) Nambu, Felipe Augusto Nery [UNIFESP]; Andréo Filho, Newton [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Papain is a proteolytic enzyme widely used in the treatment of wounds and has recently shown potential activity in promoting the absorption of drugs in the gastrointestinal tract. Solid dosage forms are an interesting option for oral administration of papain, since it provides greater stability to the enzyme due to the absence of water in the formulation. Among the solid forms the mini-tablets, together with pellets and granules, make up the group of multiparticulate systems, which has attracted attention since the mini-tablets show some advantages as a greater control of the velocity and place of release of the drug, more flexibility in the adjustment of dose, better distribution in the gastrointestinal tract (GIT) and increased bioavailability. The objective of the present study was to obtain mini-tablets with free or complex papain with β-cyclodextrin (βCD) or hydroxypropyl-β-cyclodextrin (HPβCD) for immediate release of the enzyme. The physicochemical characterization of the free and complex papain was carried out, as well as its proteolytic activity in its free and complex form. After the characterizations continued with the development of the mini-tablet formulations with the enzyme, and the dissolution profiles were evaluated in the different media. Samples of free papain, βCD and HPβCD, physical mixtures and complex were characterized by x-ray diffraction techniques, differential scanning calorimetry, scanning electron microscopy, infrared spectroscopy and intrinsic dissolution test. Scanning electron microscopy analyzes for the complexes revealed the formation of structures different from those observed for the free compounds and physical mixtures. Thermal analysis indicated an important interaction between papain and cyclodextrins, since changes in the temperatures of occurrence of endothermic events, especially for βCD, were observed. The diffractograms for papain and βCD samples showed a change of amorphous form (free papain) to crystalline form when complexed with βCD. In the proteolytic activity of free PPN, the relative activity value was 72,8 %, when complexed with βCD the relative activity was 83 % and with HPβCD 93,13 %.Through preformulation studies for the selection of the excipients for the formulation of mini-tablets were analyzed the physical and physicochemical characteristics such as density, particle size and flowability. The results allowed the choice of microcrystalline cellulose and pregelatinized starch (1: 1) as diluents and 3% of magnesium stearate and colloidal silicon dioxide (1: 1) as lubricants. After compression, formulations containing free papain, PPN-βCD and PPN-HPβCD complexes were subjected to quality control. All formulations of mini-tablets met the specifications of uniformity of weight, content, friability and hardness. It was possible to obtain mini-tablets with papain free and complexed with cyclodextrin. The formulations meet the minimum requirements for mini-tablets, the formulations being promising for the coating aiming at specific site release.
- ItemAcesso aberto (Open Access)Desenvolvimento e caracterização de filmes de desintegração oral contendo dinitrato de isossorbida(Universidade Federal de São Paulo, 2021-07-06) Silva, Larissa Léa [UNIFESP]; Rodrigues, Leticia Norma Carpentieri [UNIFESP]; http://lattes.cnpq.br/2032525648530694; http://lattes.cnpq.br/420597982875239O dinitrato de isossorbida (DNIS) é um insumo farmacêutico ativo vasodilatador, indicado para o tratamento profilático da dor isquêmica cardíaca associada à insuficiência coronariana e na crise da angina peitoral. O DNIS é intensamente metabolizado por meio do efeito de primeira passagem hepática, o que torna sua biodisponibilidade variável. Os filmes de desintegração oral sofrem rápida dispersão quando em contato com a saliva, o que resulta no aumento da biodisponibilidade, reduzindo a exposição das substâncias à degradação no trato gastrintestinal e ao metabolismo de primeira passagem hepática. Além disso, a fácil administração dos filmes de desintegração oral favorece a adesão do paciente ao tratamento. O objetivo deste trabalho foi desenvolver e caracterizar filmes de desintegração oral contendo dinitrato de isossorbida, utilizando hidroxipropilmetilcelulose (HPMC) como polímero formador de filme e hidroxipropil--ciclodextrina (HPCD) como agente solubilizante, através do método de evaporação de solvente. Os filmes foram preparados por meio de planejamento fatorial completo (32) empregando os fatores concentração de polímero (HPMC E6 1,5, 2,0, 2,5%) e natureza do plastificante (glicerina, propilenoglicol, sorbitol); e caracterizados quanto as suas propriedades físicas, físico-quimicas, mecânicas e colorimétricas. Foram comparados os perfis de dissolução entre os comprimidos sublingual de DNIS (medicamento utilizado como referência) e os filmes de desintegração oral. As curvas de difração de raios-X mostraram amorfização do DNIS/lactose (25/75, p/p) sendo sugerido a formação de complexos de inclusão multicomponentes [(DNIS:HPCD)-HPMC]. A quantidade de polímero formador de filme e a natureza do plastificante tiveram papel crítico nas propriedades mecânicas dos filmes. Maior transparência foi observada para os filmes orais preparados com o plastificante propilenoglicol. À exceção do filme F4, os perfis de dissolução médios dos filmes de desintegração oral e do medicamento de referência mostraram-se equivalentes. Os valores de eficiência de dissolução (ED) obtidos entre os filmes (F1-9) foram superiores àquele observado para o medicamento de referência (88,36±0,01%), sugerindo aumento da solubilidade do DNIS pelo complexo [(DNIS:HPCD)-HPMC]. Com base na avaliação dos efeitos obtidos a partir da caracterização dos filmes, foi possível selecionar a melhor formulação de acordo com a função desejabilidade (f_D) (0f_D 1), usando os fatores nos seus valores ótimos. O valor máximo para a função desejabilidade global (f_D) foi de 0,8522, correspondente a 2,0% de HPMC E6 e o emprego de propilenoglicol como plastificante