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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

In-vitro inhalation performance for formoterol dry powder and metred dose inhalers : in-vitro characteristics of the emitted dose from the formoterol dry powder and metred dose inhalers to identify the influence of inhalation flow, inhalation volume and the number of inhalation per dose

Alaboud, S. January 2011 (has links)
The present work aimed at assessing the dose emission and aerodynamic particle size characteristics of formoterol fumarate from Atimos Modullite, a metered dose inhaler (MDI) and Foradil Aeroliser, Easyhaler, and Oxis Turbuhaler dry powder inhalers (DPI) at different inhalation flow rates and volumes using in vitro methodology. Recognised methods have been adopted and validated to generate the results. The in vitro characteristics of formoterol were measured according to standard pharmacopeial methodology with adaptation to simulate routine patient use. The dose emission from the Atimos Modulite was determined using inhalation volumes of 4 and 2 L and inhalation flows of 10, 28.3, 60, and 90 L/min. The %nominal dose emitted was consistent between the various flow rates and inhalation volumes of 4 and 2L. The particle size distribution was measured using an Anderson Cascade Impactor (ACI) combined with a mixing inlet valve to measure particle size distribution at inhalation flow rates below 30 L/min. The particle size distribution of formoterol from Atimos Modulite was measured using inhalation flows of 15, 28.3, 50, and 60 L/min with and without different spacers, Aerochamber and Volumatic. The mean fine particle dose (%nominal dose) through an Atimos without spacer were 53.52% (2.51), 54.1% (0.79), 53.37% (0.81), 50.43% (1.92) compared to Aerochamber 63.62% (0.44), 63.86% (0.72), 64.72% (0.47), 59.96% (1.97) and Volumatic 62.40% (0.28),63.41% (0.52), 64.71% (0.61), 58.43% (0.73), respectively. A small decrease in the fine particle dose was observed as the inhalation flow increased, but this was not significant. The respective mean mass aerodynamic diameter (MMAD) increased as the flow rate was increased from 15 of 60 L/min. Results also suggests that the use of spacers provides better lung deposition for patients with problems using MDI. The dose emission from the Foradil Aeroliser was determined using inhalation volumes of 4 and 2 L, at inhalation flows of 10, 15, 20, 28.3, 60, and 90 L/min plus two inhalations per single dose. The %nominal dose emitted using 2 L inhalation volume was approximately half when compared to results obtained using inhalation volume of 4 L. A significantly (p<0.001) higher amount of drug was also emitted from Easyhaler® at inhalation volume of 4 L through flow rates of 10, 20, 28.3, 40, and 60 L/min compared 2 L. Similar results were observed through Oxis Turbuhaler at inhalation flow rates of 10, 20, 28.3, 40, and 60 L/min. Comparative studies were also carried out to evaluate the particle size distribution of formoterol through the DPIs. The nominal fine particle dose through Aeroliser using inhalation flows of 10, 20, 28.3, 60 and 90 L/min were 9.23%, 14.70 %, 21.37%, 28.93%, and 39.70% for the 4 L and 4.17%, 5.55%, 7.28%, 8.41%, and 11.08% for the 2 L, respectively. The respective MMAD significantly (p<0.001) decreased with increasing flow rates. Aeroliser performance showed significant (p<0.001) increase in the % nominal fine particle dose for two inhalations compared to one inhalation at both 4 and 2 L. The Easyhaler was measured using inhalation flows of 10, 20, 28.3, 40, 60 L/min. The nominal fine particle dose were 19.03%, 27.09%, 36.89%, 49.71% and 49.25% for the 4 L and 9.14%, 15.44%, 21.02%, 29.41%, 29.14% for the 2 L, respectively. The respective MMAD significantly (p<0.001) decreased with increasing flow rates. Easyhaler performance at both 4 and 2 L showed no significant differences between one and two inhalations at low flow rates (10, 20, 28.3), but this was significant (p<0.05) at higher flow rates (40 and 60 L/min). The Oxis Turbuhaler was also measured using inhalation flows of 10, 20, 28.3, 40, 60 L/min. The nominal fine particle dose were 12.87%, 24.51%, 28.25%, 34.61%, 40.53% for the 4 L and 8.55%, 15.31%, 21.36%, 19.53%, 22.31% for the 2 L, respectively. Turbuhaler performance showed significant (p<0.05) differences between one and two inhalations at varying flow rates 2 L inhalation volumes, but not at 4 L. The use of Foradil Aeroliser delivers small particles as the Oxis Turbuhaler using two inhalations hence delivering formoterol deep into the lungs. Also, this thesis shows that high flow resistance of Turbuhaler will indeed influence the ability of patients with severe asthma or children to use the system. Beside, Easyhaler produced the highest drug delivery to the lungs, thus, making it a more desirable system to use, especially for children and asthma sufferers.
2

In-vitro inhalation performance for formoterol dry powder and metred dose inhalers. In-vitro characteristics of the emitted dose from the formoterol dry powder and metred dose inhalers to identify the influence of inhalation flow, inhalation volume and the number of inhalation per dose.

Alaboud, S. January 2011 (has links)
The present work aimed at assessing the dose emission and aerodynamic particle size characteristics of formoterol fumarate from Atimos Modullite, a metered dose inhaler (MDI) and Foradil Aeroliser, Easyhaler, and Oxis Turbuhaler dry powder inhalers (DPI) at different inhalation flow rates and volumes using in vitro methodology. Recognised methods have been adopted and validated to generate the results. The in vitro characteristics of formoterol were measured according to standard pharmacopeial methodology with adaptation to simulate routine patient use. The dose emission from the Atimos Modulite was determined using inhalation volumes of 4 and 2 L and inhalation flows of 10, 28.3, 60, and 90 L/min. The %nominal dose emitted was consistent between the various flow rates and inhalation volumes of 4 and 2L. The particle size distribution was measured using an Anderson Cascade Impactor (ACI) combined with a mixing inlet valve to measure particle size distribution at inhalation flow rates below 30 L/min. The particle size distribution of formoterol from Atimos Modulite was measured using inhalation flows of 15, 28.3, 50, and 60 L/min with and without different spacers, Aerochamber and Volumatic. The mean fine particle dose (%nominal dose) through an Atimos without spacer were 53.52% (2.51), 54.1% (0.79), 53.37% (0.81), 50.43% (1.92) compared to Aerochamber 63.62% (0.44), 63.86% (0.72), 64.72% (0.47), 59.96% (1.97) and Volumatic 62.40% (0.28),63.41% (0.52), 64.71% (0.61), 58.43% (0.73), respectively. A small decrease in the fine particle dose was observed as the inhalation flow increased, but this was not significant. The respective mean mass aerodynamic diameter (MMAD) increased as the flow rate was increased from 15 of 60 L/min. Results also suggests that the use of spacers provides better lung deposition for patients with problems using MDI. The dose emission from the Foradil Aeroliser was determined using inhalation volumes of 4 and 2 L, at inhalation flows of 10, 15, 20, 28.3, 60, and 90 L/min plus two inhalations per single dose. The %nominal dose emitted using 2 L inhalation volume was approximately half when compared to results obtained using inhalation volume of 4 L. A significantly (p<0.001) higher amount of drug was also emitted from Easyhaler® at inhalation volume of 4 L through flow rates of 10, 20, 28.3, 40, and 60 L/min compared 2 L. Similar results were observed through Oxis Turbuhaler at inhalation flow rates of 10, 20, 28.3, 40, and 60 L/min. Comparative studies were also carried out to evaluate the particle size distribution of formoterol through the DPIs. The nominal fine particle dose through Aeroliser using inhalation flows of 10, 20, 28.3, 60 and 90 L/min were 9.23%, 14.70 %, 21.37%, 28.93%, and 39.70% for the 4 L and 4.17%, 5.55%, 7.28%, 8.41%, and 11.08% for the 2 L, respectively. The respective MMAD significantly (p<0.001) decreased with increasing flow rates. Aeroliser performance showed significant (p<0.001) increase in the % nominal fine particle dose for two inhalations compared to one inhalation at both 4 and 2 L. The Easyhaler was measured using inhalation flows of 10, 20, 28.3, 40, 60 L/min. The nominal fine particle dose were 19.03%, 27.09%, 36.89%, 49.71% and 49.25% for the 4 L and 9.14%, 15.44%, 21.02%, 29.41%, 29.14% for the 2 L, respectively. The respective MMAD significantly (p<0.001) decreased with increasing flow rates. Easyhaler performance at both 4 and 2 L showed no significant differences between one and two inhalations at low flow rates (10, 20, 28.3), but this was significant (p<0.05) at higher flow rates (40 and 60 L/min). The Oxis Turbuhaler was also measured using inhalation flows of 10, 20, 28.3, 40, 60 L/min. The nominal fine particle dose were 12.87%, 24.51%, 28.25%, 34.61%, 40.53% for the 4 L and 8.55%, 15.31%, 21.36%, 19.53%, 22.31% for the 2 L, respectively. Turbuhaler performance showed significant (p<0.05) differences between one and two inhalations at varying flow rates 2 L inhalation volumes, but not at 4 L. The use of Foradil Aeroliser delivers small particles as the Oxis Turbuhaler using two inhalations hence delivering formoterol deep into the lungs. Also, this thesis shows that high flow resistance of Turbuhaler will indeed influence the ability of patients with severe asthma or children to use the system. Beside, Easyhaler produced the highest drug delivery to the lungs, thus, making it a more desirable system to use, especially for children and asthma sufferers.
3

Improved inhalation therapies of brittle powders

Carvalho, Simone Raffa 03 March 2015 (has links)
Advancements in pulmonary drug delivery technologies have improved the use of dry powder inhalation therapy to treat respiratory and systemic diseases. Despite remarkable improvements in the development of dry powder inhaler devices (DPIs) and formulations in the last few years, an optimized DPI system has yet to be developed. In this work, we hypothesize that Thin Film Freezing (TFF) is a suitable technology to improve inhalation therapies to treat lung and systemic malignancies due to its ability to produce brittle powder with optimal aerodynamic properties. Also, we developed a performance verification test (PVT) for the Next Generation Cascade Impactor (NGI), which is one of the most important in vitro characterization methods to test inhalation. In the first study, we used TFF technology to produce amorphous and brittle particles of rapamycin, and compared the in vivo behavior by the pharmacokinetic profiles, to its crystalline counterpart when delivered to the lungs of rats via inhalation. It was found that TFF rapamycin presented higher in vivo systemic bioavailability than the crystalline formulation. Subsequently, we investigated the use of TFF technology to produce triple fixed dose therapy using formoterol fumarate, tiotropium bromide and budesonide as therapeutic drugs. We investigated applications of this technology to powder properties and in vitro aerosol performance with respect to single and combination therapy. As a result, the brittle TFF powders presented superior properties than the physical mixture of micronized crystalline powders, such as excellent particle distribution homogeneity after in vitro aerosolization. Lastly, we developed a PVT for the NGI that may be applicable to other cascade impactors, by investigating the use of a standardized pressurized metered dose inhaler (pMDI) with the NGI. Two standardized formulations were developed. Formulations were analyzed for repeatability and robustness, and found not to demonstrate significant differences in plate deposition using a single NGI apparatus. Variable conditions were introduced to the NGI to mimic operator and equipment failure. Introduction of the variable conditions to the NGI was found to significantly adjust the deposition patterns of the standardized formulations, suggesting that their use as a PVT could be useful and that further investigation is warranted. / text
4

Filme de quitosana para uso em sistema de liberação controlada de fumarato de formoterol. / Chitosan film for use in a controlled release system of formoterol fumarate.

GUEDES, Dayse de Lourdes Madruga Espínola. 04 April 2018 (has links)
Submitted by Johnny Rodrigues (johnnyrodrigues@ufcg.edu.br) on 2018-04-04T20:45:16Z No. of bitstreams: 1 DAYSE DE LOURDES MADRGA ESPÍNOLA GUEDES - DISSERTAÇÃO PPG-CEMat 2014..pdf: 2225179 bytes, checksum: ad9f795a81034cb79500cb575de58f73 (MD5) / Made available in DSpace on 2018-04-04T20:45:16Z (GMT). No. of bitstreams: 1 DAYSE DE LOURDES MADRGA ESPÍNOLA GUEDES - DISSERTAÇÃO PPG-CEMat 2014..pdf: 2225179 bytes, checksum: ad9f795a81034cb79500cb575de58f73 (MD5) Previous issue date: 2014-12-12 / A presente pesquisa tem como objetivo, caracterizar filmes de quitosana, de aplicação sublingual, para uso em sistemas de liberação controlada de fumarato de formoterol., buscando uma nova alternativa para o tratamento emergencial das crises de asma. Sabemos que a asma é uma patologia de grande incidência no Brasil e no mundo, pois existem cerca de 300 milhões de pessoas acometidas pela doença a nível mundial e 20 milhões de brasileiros .É uma doença de caráter hereditário, crônica que não tem cura e que se apresenta muitas vezes como uma emergência médica , pois nas crises da doença o socorro deve ser imediato com o intuito de evitar o óbito do paciente. Hoje utiliza-se apenas a via inalatória como preferencial para administração dos broncodilatadores, visto que essa via tem rapidez de ação. No entando, deparamo-nos com a difícil técnica de utilização dos inaladores que veiculam o medicamento o que muitas vezes impossibilita a sua utilização especialmente em crianças, idosos e pacientes muito debilidados. Vendo esta dificuldade, propusemos com o nosso trabalho buscar uma nova via de utilização dos medicamentos broncodilatadores, que tivesse a mesma eficácia da via inalatória, dispensando a difícil técnica de utilização dos fármacos .Para isso , escolhemos a via sublingual de rápida ação e facilidade de utilização, podendo ser empregada mais adequadamente em uma crise de asma . Selecionamos a quitosana, por ser um biopolímero versátil e muito utilizado em sistema de liberação controlada de fármaco para veicular o formoterol , que é um potente broncodilatador, através da produção de um filme para deposição sublingual. E os resultados obtidos através das caracterizações apresentaram membranas com variações de cristalinidade (por DRX) de acordo com o processo de reticulação, além de apresentarem uma possível relação entre reticulação e liberação. Por FTIR pode-se observar certa interação entre o fármaco e os grupos amina da quitosana, assim como possível isomerização do fármaco pela reticulação com 5% de TPP. Pelas microscopias ótica e eletrônica, pode-se observar que o acréscimo de fármaco proporcionou alguma rugosidade a membrana. Também pelas microscopias verificou-se a reticulação não homogênea da superfície da membrana. Por EDS não se verificou nenhum elemento estranho a estrutura da quitosana e do fármaco. Por medida do ângulo de molhabilidade pode-se verificar aumento do perfil hidrofílico da membrana por adição do fármaco, perfil este que não foi modificado pelo processo de reticulação. O ensaio de citotoxicidade apresentou resultados que indicam a membrana como promissora candidata a testes in vivo. / This research aims to characterize chitosan films, sublingual application, for use in controlled release of formoterol fumarate systems., Looking for a new alternative for the emergency treatment of asthma attacks. We know that asthma is a disease of high incidence in Brazil and in the world, because we have about 300milhões of people with the disease worldwide and 20 million Brazilians .It is one hereditary disease, chronic that has no cure and that often presents as a medical emergency, because the crisis of the disease the relief should be immediate in order to prevent the death of the patient. Today only is used inhalation as preferred for administration of bronchodilators, since this route has faster action .In entando, we are faced with the difficult technique for using inhalers that deliver the medicine which often makes it impossible to use especially in children, the elderly and very debilidados patients. Buy this difficulty, we proposed in our work to seek a new route for the use of bronchodilators, which had the same effectiveness of inhaled, eliminating the difficult technique of using drugs .For this, choose the sublingual route of fast action and ease of use and can be used more appropriately in an asthma attack. Chitosan selected because it is a versatile and widely used biopolymer for controlled drug delivery system for conveying formoterol, which is a potent bronchodilator, by producing a film for sublingual deposition. And the results obtained from the characterization showed membranes crystallinity variations (XRD) according to the crosslinking process, besides presenting a possible relationship between cross-linking and release. By FTIR one can observe some interaction between the drug and amino groups of chitosan, and can isomerization of drug by crosslinking with 5% TPP. Through optical and electronic microscopy, it can be seen that addition of drug has provided some roughness to the membrane. Also by microscopy verified the inhomogeneous crosslinking of the membrane surface. EDS there was no foreign object the structure of chitosan and the drug. By measuring the wetting angle can be checked increase the hydrophilic profile of the membrane by addition of the drug, this profile has not been modified by crosslinking process. The cytotoxicity assay results presented indicate that the membrane as a promising candidate for in vivo testing.

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