Submitted by Marta Toyoda (1144061@mackenzie.br) on 2018-10-09T17:18:01Z No. of bitstreams: 2 Camila Paraíso Monção.pdf: 2300400 bytes, checksum: 51d40d978d5bf3204c042eb4fbdef32b (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Paola Damato (repositorio@mackenzie.br) on 2018-11-14T13:27:04Z (GMT) No. of bitstreams: 2 Camila Paraíso Monção.pdf: 2300400 bytes, checksum: 51d40d978d5bf3204c042eb4fbdef32b (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-11-14T13:27:04Z (GMT). No. of bitstreams: 2 Camila Paraíso Monção.pdf: 2300400 bytes, checksum: 51d40d978d5bf3204c042eb4fbdef32b (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-08-10 / In this work the main characteristics, applications, potentialities and limitations of the controlled release systems were studied, as well as the mechanisms that directly influenced the release kinetics of the active agent. Micro and nanostructured systems have great potential for the controlled release and encapsulation of bioactive molecules. The various biodegradable polymer systems represent a new strategy for the delivery of active ingredients. A controlled release system enables the drug concentration profile to remain constant within the therapeutic range thereby promoting increased therapeutic index and immune response to the patient and avoiding adverse side effects when compared to conventional methods of administration. In this work were obtained membranes formed by polymeric biosystems for application in controlled release of drugs and other assets. Four release systems were obtained: beeswax / protein / lecithin; beeswax / protein / alginate / lecithin and beeswax / alginate / chitosan / lecithin by methods of complex coacervation and spray drying. The results show that the most effective system was bee / protein / alginate / lecithin. / Neste trabalho foram estudadas as principais características, aplicações, potencialidades e limitações dos sistemas de liberação controlada de farmácos, bem como os mecanismos que influenciaram diretamente a cinética de liberação do agente ativo. Os sistemas micro e nanoestruturados apresentam grande potencial para a liberação controlada e encapsulação de moléculas bioativas. Os diversos sistemas poliméricos biodegradáveis representam uma nova estratégia para a veiculação de ingredientes ativos. Um sistema de liberação controlada possibilita que o perfil de concentração da droga se mantenha constante dentro da faixa terapêutica promovendo dessa forma, aumento do índice terapêutico e da resposta imunológica ao paciente e evitando efeitos colaterais adversos quando comparado aos métodos convencionais de administração. Neste trabalho foram obtidas membranas formadas por biossitemas poliméricos para aplicação em liberação controlada de proteína concentrada do soro de leite WPC. Foram obtidos 4 sistemas de liberação: cera de abelha/proteína/lecitina; cera de abelha/proteína/alginato/lecitina e cera de abelha/alginato/quitosana/lecitina pelos métodos de coacervação complexa e spray drying. Com a simulação do pH do sistema gastrintestinal (pH 1,2 e pH 6,8) pode-se observar o tempo em que cada membrana liberou a proteína. Com esta informação concluimos o local teórico da liberação da proteína e quais membranas não são compativeis com o local de ação escolhido. Os resultados mostraram que o sistema mais efetivo foi o de cera de abelha/proteína/alginato/quitosana com liberação em pH 6,8 nas duas concentrações de proteína utilizadas 40% e 60% de proteína m/m.

Les probiotiques sont des microorganismes vivants qui, ingérés en quantité suffisante, exercent des effets positifs sur la santé. La lyophilisation est aujourd’hui questionnée quant à sa consommation d’énergie et son caractère discontinu. S’il offre une alternative pour produire massivement des poudres probiotiques à faible coût, le séchage par atomisation induit quant à lui des stress thermiques et oxydatifs conduisant à des pertes de viabilité rédhibitoires.Dans ce travail, un procédé innovant de séchage par atomisation est proposé. Du lactosérum doux concentré (jusqu’à 30% p/p) est utilisé à la fois comme support de culture et de séchage de P. freudenreichii et L. casei. Ce procédé élimine les étapes intermédiaires à risque de contamination élevé, accroît la biomasse et améliore la viabilité des bactériesLes mécanismes sous-jacents ont été explorés au plan de la résistance bactérienne et des conditions de séchage. Le milieu concentré induit une osmoadaptation des bactéries par expression de protéines de stress et accumulation de solutés compatibles, conduisant à une tolérance accrue des probiotiques à différents stress. La présence d’agrégats et la concentration en Mg2+ du milieu concentré pourraient également être impliquées.Le scale-up du procédé a été étudié : un schéma technologique semi-industriel impliquant séchage par atomisation, sur bande et en lit fluidisé a permis d’atteindre une viabilité de 100% (> 109 CFU g-1). Par ailleurs, la fonctionnalité des poudres probiotiques a été évaluée in vitro and in vivo sur modèle porcelet. Ce travail ouvre de nouvell / Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Freeze drying, the reference drying method, is currently challenged because of its low energy-efficiency and productivity. Therefore, spray drying is expected to be an alternative and sustainable method for producing probiotic powders. The issue remains in the considerable inactivation of probiotics caused by high temperature and dehydration during the process. In this work, a novel spray-drying process for continuous production of probiotics was challenged. Concentrated sweet whey (up to 30% w/w dry matter) was used to both culture and spray dry P. freudenreichii ITG P20 and L. casei BL23. This process cut down the steps between culturing and drying (e.g. harvesting, washing), increases the cell population after growth and improves spray drying productivity and probiotic viability. The mechanisms were explored from bacterial physiology and drying process conditions. The hypertonic stress led to overexpression of key stress proteins and accumulation of intracellular compatible solutes, which enhanced multistress tolerance. The presence of protein aggregates and optimal concentration of Mg2+ in matrix may also be involved.The feasibility of scaling up this process was validated. A multi-stage semi industrial drying process, coupling spray-drying with belt drying and fluid-bed drying, was applied to further improve the probiotic viability to 100% (> 109 CFU g-1). Moreover, the functionality of these probiotic powders was investigated in vitro and in viv

Chronic respiratory diseases such as asthma, COPD, pulmonary fibrosis are more prevalent throughout the world. For some of these diseases there is no cure, the current treatment options manages the symptoms and acute exacerbation. The new approach to find a curative therapy for respiratory diseases is by targeting the cellular / molecular pathways that either cause the disease or has the potential cure the disease. It becomes important to target the respiratory system in treating these diseases to increase the delivered dose and reduce the unwarranted adverse effects. Dry powder inhaler (DPI) is a targeted drug delivery dosage form commonly used to target the airways to treat respiratory diseases. There are two components to dry powder inhaler product – powdered drug formulation and inhaler device; a unified performance of the two is essential for a successful product. In this study, dry powder aerosol of novel drug compounds that targets the underlying cellular and molecular mechanism are developed for the first time. Advanced organic closed mode spray drying technique was used to the produce microparticulate/ nanoparticulate formulations. The formulation of the novel compounds involved utilizing sugar based excipients. Each formulation that was produced was comprehensively characterized in the solid state. The safety of these formulations were tested in in vitro human pulmonary cell lines. The in vitro aerosol dispersion of the spray dried drugs were tested using three FDA approved human inhaler devices. The influence of the inhaler device resistance and spray drying process conditions on the aerosol dispersion was evaluated. Preliminary testing of the formulations in in vivo animal models shows promising results in treating chronic respiratory diseases with these superior aerosol formulations.

Existe atualmente uma crescente produção de leite de búfala no Brasil e no mundo, sendo que 13% do leite mundial é produzido por esta espécie, perdendo somente para a produção do leite bovino. Esse crescimento deve-se às características peculiares do leite desta espécie em comparação ao bovino, incluindo teores mais elevados de vitamina C, minerais (como cálcio e fósforo), gordura e proteína. Uma alternativa para dar maior rentabilidade econômica ao leite consiste na transformação do produto para a forma de pó de fácil reconstituição (instantâneo) através de um processo de secagem. Como a reconstituição de um alimento em pó depende significativamente das suas características de molhabilidade, é comum a utilização de processos como aglomeração e lecitinação para melhorar a molhabilidade do leite em pó. Neste contexto, o objetivo deste estudo consiste em investigar a influência da adição de lecitina, antes da secagem por atomização, na molhabilidade do leite de búfala em pó. Com esta finalidade, o leite de búfala in natura foi semidesnatado, pasteurizado, concentrado a 40% (percentual mássico) de sólidos totais e seco por pulverização. Nos produtos preparados com lecitina, este aditivo foi utilizado em proporções de 0,3, 0,5 e 1,0 g de lecitina/100 g de sólidos totais no leite concentrado, previamente ao processo de secagem por atomização. Nestas condições, o efeito da concentração de lecitina na molhabilidade do leite em pó produzido foi avaliado através da técnica de Washburn e do teste de molhamento estático. Ainda, o material seco foi avaliado quanto ao teor de umidade, distribuição de tamanho de partículas e, para amostras específicas, quanto à área superficial, atividade de água, cor e morfologia das partículas (via microscopia eletrônica de varredura). Foi observado que a adição de lecitina diminuiu o tempo de molhamento (valores compreendidos entre 63,9 e 188,4 s) quando comparado ao leite in natura (300,9 s). O ângulo de contato das amostras de leite em pó obtidas em níveis superiores a 0,3% de lecitina adicionada diminuiu significativamente, para valores compreendidos entre 82,73 ± 2,76° e 81,21 ± 2,23°, com relação ao valor obtido sem adição do aditivo (89,01 ± 0,48°). Entretanto, a presença de lecitina não apresentou considerável influência na umidade, atividade de água, cor, morfologia, área superficial e na distribuição de tamanho das partículas obtidas. / There is nowadays a growing production of buffalo milk in Brazil and in the world. It already represents 13% of total world milk production, being second only to the production of bovine milk. This growth is due to the peculiar characteristics of this kind of milk compared to cow milk, such as higher content of vitamin C, minerals (such as calcium and phosphorous), fat and protein. An alternative to provide greater economic return from milk consists in converting the product to powder for easy reconstitution (i.e. instant food) through a drying process. As the reconstitution of a powdered food depends strongly on its characteristics of wettability, the utilization of alternatives such as agglomeration and addition of lecithin are commonly used to improve the wettability of the final product. In this context, the aim of this study is to investigate the influence of the addition of lecithin, previously to the spray drying on the wettability of buffalo milk powder. For such purpose, the fresh buffalo milk was partially-skimmed, pasteurized, concentrated to 40% (mass percent) of total solids and spray-dried. Four milk powders were produced, one without addition of lecithin and three with different contents of lecithin (0.3, 0.5 and 1.0 g of lecithin/100 g of total solids). The effect of the concentration of lecithin on the wettability of the powder produced was measured by the Washburn technique and static wetting test. Further, the dried material was analyzed for moisture content, particle size distribution, and for specific samples, for surface area, water activity, color and particle morphology (scanning electron microscopy). It was observed that the addition of lecithin decreased the wetting time (values comprised between 63.9 and 188.4 s) when compared to lecithin-free milk (300.9 s). The contact angle of the milk powder samples obtained with levels greater than 0.3% of added lecithin significantly decreased to values between 82.73 ± 2.76° and 81.21 ± 2.23°, with respect to the value obtained without addition of the additive (89.1°). However, the presence of lecithin showed no significant influence on the moisture content, water activity, color, morphology, surface area and particle size distribution of the produced powders.

Orientador: Carlos Raimundo Ferreira Grosso / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-03T15:38:52Z (GMT). No. of bitstreams: 1 Santos_AndreaBarbosa_D.pdf: 1408161 bytes, checksum: b337fedcba99a6ce63c76b73fbcea3f1 (MD5) Previous issue date: 2003 / Resumo: Neste trabalho a oleoresina de páprica oriunda de frutos maduros de pimentões (Capsicum annuum L.), foi encapsulada por processo de atomização, utilizando-se os agentes encapsulantes aglomerados porosos de grânulos de amido de arroz / gelatina e goma arábica. A extração da oleoresina encapsulada foi realizada em ultra-som durante cinco minutos em álcool etílico hidratado apresentando rendimentos de extração de 48,8 e 77,5% para os encapsulados em goma arábica, e aglomerados de amido/gelatina respectivamente. Os rendimentos em relação à retenção durante o processo de encapsulação, corrigidos pela deficiência do método de extração, foram de 100% para cápsulas de goma arábica e em torno de 89% para encapsulados de aglomerados porosos de grânulos de amido de arroz / gelatina, expressos em base úmida. A estabilidade da oleoresina livre e microencapsulada foi avaliada frente às diferentes condições de temperatura (- 18 °C; 25 ± 3°C; 50 °C) e ao efeito da luz, com parte das cápsulas sendo mantidas em ambiente sem iluminação. Em ambos ensaios cápsulas fabricadas com goma arábica apresentaram maior proteção a oleoresina de páprica quanto à perda da cor original. A morfologia da parede mostrou que a parede dos encapsulados de aglomerados porosos de grânulos de amido de arroz / gelatina apresentou porosidade e interstícios foram evidenciados na matriz individualmente e nos aglomerados; em relação as microcápsulas de goma arábica, observou-se parede contínua, sem rachaduras ou poros aparentes, mas apresentando concavidades na superfície provocadas pelo processo de secagem. A distribuição de tamanho das partículas foi unimodal, com tamanho médio de 16,0 mm para as cápsulas de goma arábica e 20,3 mm para os aglomerados porosos de grânulos de amido de arroz / gelatina. A funcionalidade das microcápsulas quanto à liberação do recheio, foi avaliada por adição a dois sistemas alimentícios, um contendo somente gel de gelatina incolor sem sabor e em outro, contendo proteína, gordura, carboidratos (bolo). A distribuição da cor foi homogênea em ambos os sistemas, ou seja, não foi verificado à formação de pontos de concentração de cor nos produtos. A avaliação sensorial foi realizada através do teste afetivo de aceitação em escala hedônica de nove pontos, em relação às formulações dos padrões de gel de gelatina e, de bolo isentas de microcápsulas e do teste de comparação da coloração pela escala estruturada mista. As notas obtidas foram altas para os dois produtos antes da ingestão, média na faixa de seis e sete para a gelatina contendo encapsulados dos aglomerados porosos de grânulos de amido de arroz/gelatina e de goma respectivamente, e média de sete e nove para os bolos / Abstract: In this study the resinous paprika oil obtained from ripe peppers (Capsicum annuum L.), was encapsulated by a spray drying process, in porous agglomerates of rice starch/gelatin and gum Arabic capsules. The process of extracting the encapsulated resinous oil was carried out by breaking the capsules by ultrasonication in a solvent (hydrated ethyl alcohol) for five minutes, showing yields of 48,8 and 77,5% when Arabic gum and starch/gelatin were used respectively. The yields during the encapsulation process with respect to the retention of resinous oil as compared to the amount added, corrected by extractions methods, was 100% for gum Arabic capsules and about 89% when starch granules were formed (wet base). The stabilities of the free and micro encapsulated resinous oils were evaluated under different temperature and light conditions (freezer - 18 °C; room temperature 25 ± 3°C; and 50°C). Exposing part of the capsules in a controlled illumination chamber and maintaining the other part in a chamber with no light tested the effect of light. In both trials (temperature and light), capsules produced with gum Arabic provided greater protection to the paprika resinous oil, with respect to loss of the original color. By morphological observations the porosity of the rice starch was apparent when this material was used as wall material, interstices being observed in the matrix both individually and when agglomerated. When gum Arabic was used as wall material, the walls of the capsules were continuous, with no apparent cracks or pores, although showing some indentations on the surface provoked by the drying process. The average size of the capsules was determined by measuring particle size, both presenting a unimodal distribution, with an average particle size of 16,0 mm for the gum Arabic capsules and 20,3 mm for the rice starch/gelatin. In order to determine the functionality of the microcapsules with respect to the liberation of the core material, the capsules were added to two food systems, a simple system containing non-colored gelatin with no added flavor, and a more complex system containing protein, fat and carbohydrate (cake mix). The color distribution was homogenous in both systems, no localized concentrations of color being noted in any of the products. A preference test with a nine point hedonic scale was used for the sensory evaluation of the gelatin formulations and the cakes, as compared to those containing no microcapsules. The scores for both products were high before tasting, in the range from 6 to 7 for the gelatin containing starch/gelatin and gum capsules respectively, and 7 and 9 for the cakes / Doutorado / Doutor em Alimentos e Nutrição

No description available.

The spray drying process is widely established in the industry worldwide. However, due to its complexity in predicting variables, the technology is often regarded as a "Black box" process. In this study, a model based on energy and mass balances is designed and validated using Matlab/Simulink software and real data from a medium-sized machinery, specifically the Production Minor manufactured by GEA NIRO S/A. Additionally, the simulation incorporates a heat recovery system based on a heat pump, and its economic feasibility is examined.The simulation is validated for a narrow range of variables and demonstrates an accuracy of approximately 95% in most cases.The heat recovery system achieves an average natural gas savings of 0.43 kg/h. However, this saving is accompanied by an additional electrical consumption of 2.1 kW resulting from the operation of the heat pump.The economic feasibility study of the heat recovery system reveals an extra production cost of 0.1€/h in exchange for a 36% average reduction in natural gas dependency.

The objective of this research is to further define the relationship between the charge state of insulin, and the self assembly properties of insulin and PEGylated insulin in solution. Polyethylene glycol (PEG) chains were covalently attached to insulin in order to evaluate their impact on insulin¿s systemic duration of action after pulmonary dosing. This thesis will focus on the assembly properties of the PEG-insulin and insulin, and also demonstrate how the charge state, which was modified by the covalent attachment of PEG, relates to different modes of behavior by anion and cation exchange chromatography. In addition, explain how modifying the assembly state extends to improving formulation properties of spray-dried insulin powders. This thesis is an investigation into the relationship of insulin¿s charge state controlled by pH and how the charge state affects the self assembly of insulin, especially when the zinc ion is removed. Ionic interaction is one of the major forces affecting insulin assembly. The theory that a change in the charge state of insulin could modulate the ionic interaction and reduce hexamer formation at alkaline conditions was investigated. Experiments were designed to measure the level of hexamer with light scattering, and the amount of hexamer was then correlated with the pH and zinc content of the solutions. The importance of the charge state of the monomer and its behavior extends to chromatography and purification modes as well. Specifically, the purification of various species of PEGylated insulin presents a challenge. By varying mobile phase pH which induces the charge to insulin, an ion exchange method demonstrated very high resolution and controllable interaction between the ion exchange media and the insulin derivatives. A highly accurate method for determining molecular weight and thus the average associated state of insulin in solution has been developed using the MALS (Multi-Angle Light Scattering). Insulin concentration, pH, and metal ion concentrations, were in pharmaceutically relevant ranges. The MALS method was developed to evaluate how the parameters above affect the self-assembly properties of insulin, and use the assembly properties to improve formulations of insulin or PEGylated insulin. To use the light scattering technique the dn/dc (change in refractive index with change in concentration) is required. During the method development, the dn/dc of insulin was measured at 690 nm, and a value of 0.185 mL/g based on theory was confirmed. A novel approach for preparing insulin powders with improved chemical stability, based on maintaining the dissociation of hexamers in solution during the spray drying process was developed. The mode presented here is to remove the zinc ions from solution, increase the pH from 6.6 to 7.8, and maintain a low concentration of insulin approximately 2 to 15 mg/mL. Each of these factors alone decreases the hexamer population in solution, but by combining all three factors, hexamers are driven to very low levels of equilibrium. The increased stability of the powders is predominately related to the decrease in covalent insulin dimer (CID). The data presented correlates a reduced hexamer population in the solution with lower levels of CID¿s in the dry powder compared to controls. The CID formation rate was reduced by 40% compared to a control.

This thesis investigates enhancing the thermal stabilization of a human type 5 adenoviral vector (AdHu5) through spray drying. The spray drying process was used to dry and effectively immobilize the AdHu5 within a mixture of carbohydrate or amino acid excipients into a powder form, resulting in significantly increased thermal stabilization of the viral vector. Spray dried powders were characterized by scanning electron microscopy, differential scanning calorimetry, Karl Fischer titrations, X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) to identify the effects of temperature and atmospheric moisture on the immobilizing matrix. The best performing spray dried powder in terms of thermal stability consisted of an excipient blend of mannitol and dextran. Response surface methodology was employed to optimize production of these mannitol/dextran powders; measured responses were those relevant to industrial processing of a therapeutic material, namely powder yield for maximizing quantity, particle size for maximizing production of inhalation-deliverable powders, and adenoviral vector response for minimizing the loss of therapeutic activity. The spray drying process parameters of inlet temperature, spray gas flow rate, liquid feed rate and solute concentration in the feed were optimized resulting in a powder yield of 90%, percentage of ideally-sized particles of 50% and a near-zero viral vector titre loss of 0.25 log loss median tissue culture infectious dose (TCID50). The spray dried mannitol/dextran powders proved to have exceptional thermal stability during long term storage as minimal viral vector activity loss was observed when stored at 20°C for 90 days at low relative humidity (0.7 ± 0.3 log TCID50) in comparison to the liquid control which exhibited complete activity loss under the same storage conditions. Furthermore, viral activity of mannitol/dextran powders was retained over short term exposure (72 hours) to temperatures as high as 55°C whereas the liquid control expectedly lost all AdHu5 activity after 30 minutes. Overall, this work provides a guideline for the production of thermally stable powders and active biopharmaceuticals, such as AdHu5 vectors for vaccine applications, using the spray drying process. / Thesis / Master of Applied Science (MASc) / Many vaccines and their base components inherently deteriorate in function at moderate temperatures. Storage by refrigeration at temperatures ranging between 4°C and -80°C is the norm. Such refrigeration is costly for long term storage and significantly limits where vaccines can be sent. This reduces the availability of vaccines in locations around the world where these storage conditions are infeasible but vaccines are needed most. Spray drying, a process which forms dry powders from solution, was used; the solution contained sugars or amino acids to surround and protect the sensitive vaccine component. The produced powders from this work exhibited enhanced thermal stability compared to the control, reducing the need for refrigeration during storage and transport. The spray drying process was further optimized for industrial use by maximizing the amount of powder recovered and ensuring the particle size was appropriate for inhalable use, but most importantly, minimizing losses in therapeutic effectiveness during processing. This production of a thermally stable vaccine is advantageous because is allows for better world-wide accessibility and reduces overall production and delivery costs.

No description available.