Resumen:

Beads are one of the particulate delivery systems used to achieve protection and/or controlled delivery of different active ingredients or microorganisms. Polyvinyl alcohol is a non-toxic and biodegradable polymer and possesses extensive applications as a biomaterial. In the present work, two different strategies were applied for the prediction of shape and size of polyvinyl alcohol beads. These beads were obtained by extrusion dripping of a boric acid?polyvinyl alcohol aqueous solution into a basic aqueous gelling bath. The shapes and sizes of immature, mature and dry beads were determined using optical microscopy. Two different strategies included statistical and fluid dynamical (mechanistic) models to fit the experimental data. The shape of immature and mature beads was found to be dependent on the viscosity of the dripping solution for the former and the maturation time for the latter. The shape of dry beads was found to be mainly dependent on the particle contraction in the drying process. The size of mature and dried beads was correctly predicted from the operating conditions by means of a statistically developed model and from the dripping solution properties by means of a fluid dynamical approach. The optimal conditions for minimal dried bead size were calculated. The obtained mathematical models allow reduction in the amount of resources and time taken in the initial stages of the development of a novel encapsulated formulation. The mechanistic model may be applied to other polymeric systems once the corresponding parameters have been determined during proof-of-concept experiments.

Afiliación de los autores: Weibel, Mario Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Afiliación de los autores: Mengatto, Luciano Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Afiliación de los autores: Rintoul, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Afiliación de los autores: Luna, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Resumen:

El estudio de los procesos de absorción – liberación de 17beta-estradiol a través de fragmentos de epidermis humana y a través de membranas de quitosan, fue la base para el desarrollo de un sistema de administración transdermal de estradiol. Para realizar los estudios de estos procesos se trabajó con la celda vertical de Franz y un equipo para ensayos de disolución. Se caracterizaron los dos reactivos claves para el desarrollo de esta tesis: Quitosan y 17beta-estradiol. Se obtuvieron fragmentos de epidermis humana a partir de piel completa y se utilizaron en estudios de absorción. Los ensayos de absorción en celda de Franz y de liberación – absorción en el equipo para ensayos de disolución, permitieron la determinación de los valores de flujo de 17beta-estradiol en los fragmentos de epidermis. Se preparó una membrana de quitosan con propiedades de permeabilidad similares a epidermis humana. Las membranas de quitosan utilizadas fueron caracterizadas. Se obtuvo información sobre la interacción quitosan – 17beta-estradiol con el objeto de comprender el o los mecanismos de transporte de la droga a través o desde membranas del polímero. En las membranas con distintos tiempos de entrecruzamiento se identificaron dos tipos de microporos, hidrofílicos e hidrofóbicos. Se prepararon films de quitosan como prototipos de sistemas de administración transdermal. Se realizaron ensayos de liberación con estos sistemas, solos y junto con la membrana que simula epidermis humana. El prototipo presentó una equivalencia con el parche comercial.

The study of 17beta-estradiol absorption - release processes through human skin epidermis and chitosan membranes, was the basis for the development of an estradiol transdermal delivery system. Experiments were conducted using vertical Franz diffusion cell and dissolution test equipment. The most important reagents were characterized: Chitosan and 17beta-estradiol. Epidermis was separated from full skin. Diffusion studies with epidermis allowed to the 17beta-estradiol flux determination. An optimized chitosan membrane as a mimic of human epidermis was prepared. Chitosan membranes were characterized. Information about chitosan – 17beta-estradiol relationship was obtained in order to understand mass transport phenomena through or from polymer membranes. Hydrophilic and hydrophobic micropores were identified in cross-linked membranes prepared with different cross-linking times. Chitosan films were prepared as a prototype of transdermal delivery system. These films were tested alone and attached to the optimized chitosan membrane. Results were comparable to that obtained with a commercial patch.

Consejo Nacional de Investigaciones Científicas y Técnicas

Laboratorio Industrial Farmacéutico Sociedad del Estado

Agencia Nacional de Promoción Científica y Tecnológica

Universidad Nacional del Litoral

Resumen:

The parameters affecting the sol/gel transition of chitosan-based thermogelling systems, their final proper-ties and structure have been reported. Nevertheless, equa-tions that define this relationship specific for a particular case have not been developed. The aim of this study was to develop these equations for a general formulation without drugs, so they could be used in the preparation of different drug delivery systems. First, a factorial design was built to evaluate the main factors affecting the pH of a gel-forming solution, gelling time at ambient temperature and 37.5 °C and residual mass after exposure to a buffer solution. The analyzed independent factors were: chitosan concentration, β-glycerophosphate concentration, mixing temperature and mixing time. Mixing time was the only factor whose effect on the responses was not significant; the other three factors were considered for the optimization study. Then, a central composite design based on response surface methodology was carried out to develop statistical models which describe the relationship between active independent factors and the studied responses. The optimized gel was prepared and characterized. FTIR experiments showed that hydrogen bonds and electrostatic attraction were the main types of interactions following sol-to-gel transition. The most important finding of this investigation was that the resulting equations could be used to prepare gel-forming solutions with the desired pH, gelling time and residualmass. The significance of these equations was considered in their potential use to design hydrogels intended for con-trolled drug delivery.

Afiliación de los autores: Mengatto, Luciano Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Afiliación de los autores: Pesoa, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Afiliación de los autores: Velazquez, Natalia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Afiliación de los autores: Luna, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Resumen:

A study was carried out to compare the performance of a commercial method (MGIT) and four inexpensive drug susceptibility methods: nitrate reductase assay (NRA), microscopic observation drug susceptibility (MODS) assay, MTT test, and broth microdilution method (BMM). A total of 64 clinical isolates of Mycobacterium tuberculosis were studied. The Lowenstein-Jensen proportion method (PM) was used as gold standard. MGIT, NRA, MODS, and MTT results were available on an average of less than 10 days, whereas BMM results could be reported in about 20 days. Most of the evaluated tests showed excellent performance for isoniazid and rifampicin, with sensitivity and specificity values > 90%. With most of the assays, sensitivity for ethambutol was low (62-87%) whereas for streptomycin,sensitivity values ranged from 84 to 100%; NRA-discrepancies were associated with cultures with a low proportion of EMB-resistant organisms while most discrepancies with quantitative tests (MMT and BMM) were seen with isolates whose minimal inhibitory concentrations fell close the cutoff. MGIT is reliable but still expensive. NRA is the most inexpensive and easiest method to perform without changing the organization of the routine PM laboratory performance. While MODS, MTT, and BMM, have the disadvantage from the point of view of biosafety,they offer the possibility of detecting partial resistant strains. This study shows a very good level of agreement of the four low-cost methods compared to the PM for rapid detection of isoniazid, rifampicin and streptomycin resistance (Kappa values > 0.8); more standardization is needed for ethambutol.Mycobacterium tuberculosis were studied. The Lowenstein-Jensen proportion method (PM) was used as gold standard. MGIT, NRA, MODS, and MTT results were available on an average of less than 10 days, whereas BMM results could be reported in about 20 days. Most of the evaluated tests showed excellent performance for isoniazid and rifampicin, with sensitivity and specificity values > 90%. With most of the assays, sensitivity for ethambutol was low (62-87%) whereas for streptomycin,sensitivity values ranged from 84 to 100%; NRA-discrepancies were associated with cultures with a low proportion of EMB-resistant organisms while most discrepancies with quantitative tests (MMT and BMM) were seen with isolates whose minimal inhibitory concentrations fell close the cutoff. MGIT is reliable but still expensive. NRA is the most inexpensive and easiest method to perform without changing the organization of the routine PM laboratory performance. While MODS, MTT, and BMM, have the disadvantage from the point of view of biosafety,they offer the possibility of detecting partial resistant strains. This study shows a very good level of agreement of the four low-cost methods compared to the PM for rapid detection of isoniazid, rifampicin and streptomycin resistance (Kappa values > 0.8); more standardization is needed for ethambutol.

Afiliación de los autores: Mengatto, Luciano Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Instituto de Salud "Dr. C. G. Malbran". Instituto Nacional de Enfermedades Respiratorias; Argentina

Afiliación de los autores: Chiani, Yosena. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Instituto de Salud "Dr. C. G. Malbran". Instituto Nacional de Enfermedades Respiratorias; Argentina

Afiliación de los autores: Imaz, Maria Susana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Instituto de Salud "Dr. C. G. Malbran". Instituto Nacional de Enfermedades Respiratorias; Argentina

Resumen:

Chitosan membranes with different cross-linking density were prepared by modifying cross-linking time. Sodium tripolyphosphate was the cross-linking agent. A pulsed nuclear magnetic resonance study was performed on uncross-linked and cross-linked membranes. Different fraction of water molecules were identified in different zones within the membranes. The ratio of water molecules per chitosan repeating unit were calculated. A maximum of twelve water molecules were tightly coordinated to the chitosan repeating unit. Also, a very small water molecule fraction was identified but it was mobile enough as not to contribute to the dipolar interactions. The cross-linking reaction could lead to the formation of hydrophilic and hydrophobic interactions. These two types of interactions could result in the coexistence of a network formed by hydrophilic and hydrophobic micropores. This knowledge could be useful for the interpretation of results of hydrophobic drugs permeation across hydrophilic membranes. For example, the increment of estradiol fluxes across chitosan membranes with an increase in cross-linking density.

Afiliación de los autores: Mengatto, Luciano Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química (i); Argentina. Universidad Nacional del Litoral; Argentina

Afiliación de los autores: Ferreyra, Maria Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química (i); Argentina. Universidad Nacional del Litoral; Argentina

Afiliación de los autores: Rubiolo, Amelia Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química (i); Argentina. Universidad Nacional del Litoral; Argentina

Afiliación de los autores: Rintoul, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química (i); Argentina. Universidad Nacional del Litoral; Argentina

Afiliación de los autores: Luna, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química (i); Argentina. Universidad Nacional del Litoral; Argentina

Resumen:

Chitosan membranes with different cross-linking density were prepared by modifying cross-linking time. Sodium tripolyphosphate was the cross-linking agent. A pulsed nuclear magnetic resonance study was performed on uncross-linked and cross-linked membranes. Different fraction of water molecules were identified in different zones within the membranes. The ratio of water molecules per chitosan repeating unit were calculated. A maximum of twelve water molecules were tightly coordinated to the chitosan repeating unit. Also, a very small water molecule fraction was identified but it was mobile enough as not to contribute to the dipolar interactions. The cross-linking reaction could lead to the formation of hydrophilic and hydrophobic interactions. These two types of interactions could result in the coexistence of a network formed by hydrophilic and hydrophobic micropores. This knowledge could be useful for the interpretation of results of hydrophobic drugs permeation across hydrophilic membranes. For example, the increment of estradiol fluxes across chitosan membranes with an increase in cross-linking density

Afiliación de los autores: Mengatto, Luciano Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química (i); Argentina

Afiliación de los autores: Ferreyra, Maria Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química (i); Argentina

Afiliación de los autores: Rubiolo, Amelia Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química (i); Argentina

Afiliación de los autores: Rintoul, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química (i); Argentina

Afiliación de los autores: Luna, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química (i); Argentina

Resumen:

Chitosan membranes were obtained by a casting/solvent evaporation method and cross-linking with sodium tripolyphosphate. The effect of cross-linking time was studied and the cross-linked membranes were characterized with respect to equilibrium water content, sodium content, IR spectroscopy and permeability to a model drug (Estradiol). Sodium content increased with increasing cross-linking time. Equilibrium water content was higher in the membrane with the lowest cross-linking time. This membrane also showed a higher flux of Estradiol compared with the other which exhibited an increment in equilibrium water content and flux of Estradiol with the increase in cross-linking duration. These dissimilar results could be explained by a significant correlation between the hydrophilicity of the membrane and the hydrophobicity of Estradiol.

Afiliación de los autores: Mengatto, Luciano Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Afiliación de los autores: Luna, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Afiliación de los autores: Cabrera, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Resumen:

In this work, a new recyclable ethylene-vinyl acetate (EVA)-based strip impregnated with amitraz (AMZ) was prepared, characterized, and evaluated for the treatment of Apis mellifera against Varroa destructor. Bees are important for natural pollination, honey, and related goods production. Varroa destructor is currently considered one of the major pests and important efforts around the world are focused on methods for varroasis treatment. The procedure of strips preparation presented in this work consisted of two steps: impregnation and molding of impregnated pellets. Differential scanning calorimetryand gas chromatography?mass spectrometry analyses confirmed that AMZmolecule resisted the impregnation and molding conditions. The strips were sufficiently strong to resist destruction by the bees. The final infestation was lower in the hives treated with AMZ/EVA strips than in those treated with commercial strips. In order to check the possibility of recycling, strips were cut into little pieces and were subjected to total AMZ extraction. Finally, the fragments were exposed to re-impregnation and molding. The strips prepared after the recycling process presented the same shape and AMZ load than fresh strips.

Afiliación de los autores: Karp, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Afiliación de los autores: Luna, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Afiliación de los autores: Mengatto, Luciano Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Resumen:

In this work, a new recyclable ethylene-vinyl acetate (EVA)-based strip impregnated with amitraz (AMZ) was prepared, characterized, and evaluated for the treatment of Apis mellifera against Varroa destructor. Bees are important for natural pollination, honey, and related goods production. Varroa destructor is currently considered one of the major pests and important efforts around the world are focused on methods for varroasis treatment. The procedure of strips preparation presented in this work consisted of two steps: impregnation and molding of impregnated pellets. Differential scanning calorimetry and gas chromatography?mass spectrometry analyses confirmed that AMZ molecule resisted the impregnation and molding conditions. The strips were sufficiently strong to resist destruction by the bees. The final infestation was lower in the hives treated with AMZ/EVA strips than in those treated with commercial strips. In order to check the possibility of recycling, strips were cut into little pieces and were subjected to total AMZ extraction. Finally, the fragments were exposed to re-impregnation and molding. The strips prepared after the recycling process presented the same shape and AMZ load than fresh strips.

Afiliación de los autores: Karp, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Afiliación de los autores: Luna, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Afiliación de los autores: Mengatto, Luciano Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Resumen:

The present work deals with the study of estradiol permeation in chitosan membranes. A fractional factorial design was built for the determination of the main factors affecting estradiol permeation. The independent factors analysed were: concentration of chitosan, concentration of cross-linking agent, cross-linking time and thermal treatment. It was found that concentration of chitosan and cross-linking time significantly affected the response. The effects of thermal treatment and concentration of cross-linking agent were not significant. An optimization process based on response surface methodology was carried out in order to develop a statistical model which describes the relationship between active independent variables and estradiol flux. This model can be used to find out a combination of factor levels during response optimization. Possible options for response optimization are to maximize, minimize or move towards a target value.

Afiliación de los autores: Mengatto, Luciano Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Afiliación de los autores: Cabrera, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico Para la Industria Química; Argentina

Afiliación de los autores: Luna, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico Para la Industria Química; Argentina