Chan, Ka Man Carmen. / "October 2009." / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 160-165). / Abstracts in English and Chinese. / Table of Contents --- p.I / Acknowledgements --- p.IV / Abstract --- p.V / Abstract (Chinese version) --- p.VIII / List of Figures --- p.X / List of Tables --- p.XVIII / Chapter Chapter One. --- Introduction / Chapter 1.1 --- Pulmonary drug delivery --- p.1 / Chapter 1.2 --- Inhalation drug delivery systems --- p.4 / Chapter 1.3 --- Dry powder inhalation aerosols --- p.5 / Chapter 1.3.1 --- Principle of operation of DPIs --- p.5 / Chapter 1.3.2 --- Aerodynamic diameter --- p.6 / Chapter 1.3.2.1 --- Fine particle fraction --- p.8 / Chapter 1.3.3 --- Dispersibility --- p.8 / Chapter 1.3.4 --- Factors that affect dispersibility --- p.9 / Chapter 1.3.4.1 --- Particle Size --- p.9 / Chapter 1.3.4.2 --- Particle Density and Morphology --- p.10 / Chapter 1.3.4.3 --- Interparticulate interactions一Cohesion and adhesion --- p.11 / Chapter 1.3.4.3.1 --- Surface energetics --- p.11 / Chapter 1.3.4.3.2 --- Effect of hygroscopicity and electrostatic charges --- p.12 / Chapter 1.4 --- Particle formation techniques for DPI formulation --- p.14 / Chapter 1.4.1 --- Spray-drying --- p.14 / Chapter 1.4.2 --- Surface modification --- p.16 / Chapter 1.5 --- Physical characterization --- p.17 / Chapter 1.5.1 --- Laser diffraction --- p.17 / Chapter 1.5.2 --- X-ray powder diffraction --- p.18 / Chapter 1.5.3 --- Thermal analysis --- p.19 / Chapter 1.5.4 --- Particle morphology and surface area --- p.20 / Chapter 1.5.5 --- In vitro aerosol performance --- p.21 / Chapter 1.6 --- Surface characterization --- p.21 / Chapter 1.6.1 --- X-ray photoelectric spectroscopy (XPS) --- p.21 / Chapter 1.6.2 --- Inverse gas chromatography --- p.22 / Chapter 1.7 --- Atomic force microscopy in pharmaceutical science --- p.23 / Chapter 1.7.1 --- Principle of operation --- p.24 / Chapter 1.7.1.1 --- Tapping mode --- p.27 / Chapter 1.7.1.2 --- Contact mode --- p.27 / Chapter 1.8 --- Scope of thesis --- p.29 / Chapter Chapter Two. --- Materials and Methods / Chapter 2.1 --- Materials --- p.32 / Chapter 2.2 --- Methods --- p.32 / Chapter 2.2.1 --- Optimization of spray-drying parameters --- p.32 / Chapter 2.2.2 --- Preparation of spray-dried salbutamol sulphate powders containing different concentrations of amino acid additive --- p.33 / Chapter 2.2.3 --- Physical characterization of spray-dried powders --- p.34 / Chapter 2.2.3.1 --- Particle size and size distribution --- p.34 / Chapter 2.2.3.2 --- Specific surface area --- p.35 / Chapter 2.2.3.3 --- X-ray powder diffraction --- p.35 / Chapter 2.2.3.4. --- Scanning electron microscopy --- p.36 / Chapter 2.2.3.5. --- Thermal analysis --- p.36 / Chapter 2.2.3.5.1 --- Thermogravimetric analysis (TGA) --- p.36 / Chapter 2.2.3.5.2 --- Differential scanning calorimetry (DSC) --- p.36 / Chapter 2.2.3.6 --- Water vapour sorption isotherm --- p.37 / Chapter 2.2.3.7 --- Density measurements --- p.37 / Chapter 2.2.3.8 --- In vitro particle deposition (MSLI) --- p.38 / Chapter 2.2.4 --- Surface characterization of the spray-dried powders --- p.39 / Chapter 2.2.4.1 --- X-ray photoelectric spectroscopy (XPS) --- p.39 / Chapter 2.2.4.2 --- Surface energy measurement by inverse gas chromatography (IGC) --- p.40 / Chapter 2.2.4.2.1 --- Calculation of standard free energy of adsorption --- p.41 / Chapter 2.2.4.2.2 --- Dispersive component of surface free energy and related thermodynamic parameters --- p.42 / Chapter 2.2.4.2.3 --- Specific interactions and associated acid-base properties --- p.43 / Chapter 2.2.5. --- Atomic Force Microscopy (AFM) --- p.43 / Chapter 2.2.5.1. --- Imaging --- p.43 / Chapter 2.2.5.2. --- Force measurements --- p.44 / Chapter 2.2.5.2.1 --- Adhesion force measurements --- p.44 / Chapter 2.2.5.2.2 --- Force curve data conversions --- p.44 / Chapter Chapter Three. --- "Optimal Spray-drying Conditions, Physical Characterization and Aerosol Performance of Additive-modified Spray-dried Salbutamol Sulphate particles" / Chapter 3.1 --- Optimization of spray-drying conditions --- p.46 / Chapter 3.2 --- Effect of phenylalanine on the spray-dried SS particles --- p.52 / Chapter 3.2.1. --- Phenylalanine as the additive --- p.52 / Chapter 3.2.1.1 --- In vitro aerosol performance --- p.53 / Chapter 3.2.1.2 --- Particle morphology --- p.55 / Chapter 3.2.1.3 --- Crystallinity --- p.62 / Chapter 3.2.1.4 --- Particle size distribution and specific surface area --- p.63 / Chapter 3.2.1.5 --- Density --- p.65 / Chapter 3.2.1.6 --- Thermal analysis --- p.66 / Chapter 3.2.1.7 --- Water vapour isotherm --- p.70 / Chapter 3.3 --- Effect of leucine on the spray-dried SS particles --- p.77 / Chapter 3.3.1. --- L-Leucine as the additive --- p.77 / Chapter 3.3.1.1 --- In vitro aerosol performance --- p.78 / Chapter 3.3.1.2 --- Particle morphology --- p.80 / Chapter 3.3.1.3 --- Crystallinity --- p.86 / Chapter 3.3.1.4 --- Particle size distribution and specific surface area --- p.87 / Chapter 3.3.1.5 --- Density --- p.90 / Chapter 3.3.1.6 --- Thermal analysis --- p.92 / Chapter 3.3.1.7 --- Water vapour isotherm --- p.95 / Chapter Chapter Four. --- Surface Characterization of Additive-modified Spray-dried Salbutamol Sulphate Particles / Chapter 4.1 --- X-ray photoelectric spectroscopy --- p.103 / Chapter 4.1.1 --- Phenylalanine --- p.103 / Chapter 4.1.2 --- Leucine --- p.104 / Chapter 4.2 --- Inverse gas chromatography --- p.105 / Chapter 4.2.1 --- Phenylalanine --- p.105 / Chapter 4.2.2 --- Leucine --- p.107 / Chapter 4.3 --- Atomic force microscopy --- p.109 / Chapter 4.3.1 --- Surface topography --- p.109 / Chapter 4.3.2 --- Adhesive force measurements --- p.118 / Chapter Chapter Five. --- Conclusions and Suggestions for Future Works / Chapter 5.1 --- Conclusions --- p.139 / Chapter 5.1.1 --- Physical properties --- p.139 / Chapter 5.1.2 --- Surface characteristics and aerosol performance --- p.140 / Chapter 5.2 --- Future studies --- p.142 / Appendix --- p.143 / References --- p.160

Estudamos o efeito do tratamento com salbutamol em dois regimes: diário (DS) e administrado a intervalos de 96 horas (IS) em camundongos balb/c sensibilizados com injeções intraperitoneais de uma solução de ovoalbumina (OVA) adsorvida em hidróxido de alumínio, e desafiada com inalações de ovoalbumina a 1%. O grupo controle SAL recebeu injeções i.p. de salina e desafios inalatórios de sallina. A partir do 34o dia, os animais OVA foram tratados com salbutamol via inalatória 10 mg/ml durante 15 minutos nos dois regimes descritos. Os animais foram sacrificados no 60o dia, que corresponde a 48 horas após o último desafio antigênico. Após os camundongos serem anestesiados com pentobarbital sódico via i.p., eles foram traqueostomizados e entubados e sacrificados com secção da Aorta abdominal. Então, procedeu-se com a coleta do lavado broncoalveolar para a quantificação de leucócitos. Coletamos os tecidos pulmonares para a avaliação do processo inflamatório por quantificação de células linfomononucleares (LMN) e eosinófilos EPO+, essa última com marcação citoquímica. Além disso, estudamos a influência do tratamento adrenérgico sobre o IgE anafilático. O modelo de inflamação (grupo OVA) produziu significativo aumento do número de células totais, de eosinófilos e de neutrófilos observados na avaliação de lavado broncoalveolar. Além disso, houve nesse grupo processo inflamatório na parede de vias aéreas, caracterizada por um infiltrado linfomononuclear e com presença de eosinófilos. O nosso processo de indução de inflamação também recrutou eosinófilos para o septo alveolar. O tratamento com salbutamol diário produziu uma queda significativa do processo inflamatório no BAL, principalmente de neutrófilos e eosinófilos, enquanto que o tratamento intermitente produziu redução significativa apenas de neutrófilos. O tratamento com salbutamol a cada 96 horas (IS) promoveu uma queda significativa de células LMN quantificadas no septo alveolar, mas não atingindo valores do grupo salina (NS). Ambos os tratamentos com salbutamol produziu redução significativa de células EPO+ no parênquima pulmonar (P < 0,05). Apesar das alterações no processo celular, o salbutamol não influenciou na expressão de anticorpos IgE anafiláticos a OVA. Assim, podemos concluir que o salbutamol apresenta atividade imunomoduladora, observada por redução de eosinófilos no BAL e no parênquima pulmonar, apesar de não atingir valores semelhantes aos animais do grupo salina / We studied the effects of salbutamol treatment in two regimen: diary (DS) and at interval of 96 hours (IS) in ovalbumin sensitized (OVA) balb/c mice. The control group (NS) received i.p. injections and aerosol challenge with normal saline. Starting at day 34 the OVA animals were treated with 10mg/ml salbutamol by inhalation during 15 minutes per day in both regimen: DS and IS. The mice were sacrificed at day 60 that corresponded the fourthly eight hours after last OVA and/or salbutamol exposure. At experimental day, mice were anesthetized with i.p. injection of sodium pentobarbital, tracheostomized, entubed and the abdominal aorta sectioned. We followed with collecting of bronchoalveolar lavage (BAL) and lungs to histopathology studies. In the BAL, total cells and differential leukocytes were quantified, while in the lung sections, the EPO+ and LMN in airways wall and parenchyma septa were evaluated. Also, we sampled the blood to evaluate the effects of salbutamol on anaphylactic IgE antibodies expression. The inflammatory model (OVA animals) produced a significant increase of BAL total cells, BAL eosinophils and neutrophils, and LMN cells and EPO+ eosinophils in the airways and in the parenchyma. Diary salbutamol treatment decrease significantly BAL eosinophils and neutrophils, while the IS group showed a diminution of BAL neutrophils and LMN cells in the alveolar septum. Both salbutamol treatments produced significant decline of EPO+ cells in the lung parenchyma. Despite the changes in the cellular patterns, the salbutamol did not affect the IgE antibodies expression. So, we can concluded that salbutamol present an immunomodulatory activity observed by reduction of eosinophils in the BAL and lung parenchyma, but did not achieve the values of saline control group

INTRODUÇÃO: A dosagem ideal de salbutamol através de inaladores dosimetrados para o tratamento da asma aguda na infância não está bem estabelecida. Este estudo visou comparar dois regimes de dosagem de salbutamol via inalador dosimetrado com espaçador em crianças com crises moderadas ou graves de asma. As hipóteses deste estudo foram: I. Pacientes em vigência de crises de sibilância moderadas ou graves necessitam doses de salbutamol maiores que as até recentemente recomendadas pelo Global Initiative for Asthma (GINA). II. Doses maiores de salbutamol são seguras para crianças com idade igual ou superior a dois anos de idade. OBJETIVOS: I. Avaliar a eficácia (principalmente tempo de permanência na sala de emergência e taxas de internação hospitalar) de um regime de doses maiores de salbutamol em comparação com as até recentemente recomendadas pelo GINA. II. Verificar a segurança destas dosagens de salbutamol através do monitoramento de possíveis efeitos colaterais e dos níveis plasmáticos desta droga. MÉTODOS: Este foi um estudo prospectivo, randomizado, duplo-cego e controlado realizado em salas de emergência de três centros na cidade de São Paulo. Foram incluídos pacientes com 2-17 anos de idade com asma aguda moderada a grave (escore PRAM, Pediatric Respiratory Assessment Measure, >= 5). As dosagens de salbutamol via inalador dosimetrado com espaçador administradas durante a primeira hora foram: 6 (até 25 kg) ou 12 jatos ( > 25 kg) no grupo controle e 9 (até 15 kg), 12 ( > 15 a 20 kg), 15 ( > 20 a 25 kg) ou 18 jatos ( > 25 kg) no grupo estudo. Cada jato continha 100 mcg de salbutamol. Os pacientes dos dois grupos receberam corticosteroides e brometo de ipratrópio. Os desfechos principais do estudo foram o tempo de permanência na sala de emergência para os pacientes não internados e a necessidade ou não de internação hospitalar. Os desfechos secundários foram: mudança no volume expiratório forçado no primeiro segundo (VEF1) após uma hora, mudanças no escore PRAM, na oximetria de pulso e na frequência respiratória após uma hora e no tempo final (momento da alta ou internação hospitalar, máximo de quatro horas) e a necessidade de tratamentos adicionais após a primeira hora. Os desfechos de segurança incluíram mudanças nos níveis séricos de potássio, glicose, bicarbonato e pH no tempo final em relação ao tempo inicial, bem como possíveis anormalidades no eletrocardiograma, níveis plasmáticos de salbutamol, mudanças na frequência cardíaca e presença ou ausência de tremores, os dois últimos após uma hora e no tempo final. RESULTADOS: Foram incluídos 119 pacientes com condições basais semelhantes e não foram observadas diferenças significativas entre os grupos no tempo de permanência na sala de emergência (p=0.55) ou nas taxas de internação hospitalar (p=0.48). Não foram observadas diferenças significativas entre os grupos nas mudanças de VEF1 após uma hora, nas mudanças de escore PRAM, na oximetria de pulso e na frequência respiratória após uma hora e no tempo final. Não houve diferenças significativas entre os grupos na necessidade de tratamentos adicionais administrados após a primeira hora. Não foram observadas diferenças significativas nos desfechos de segurança entre os grupos. CONCLUSÕES: O uso de doses maiores de salbutamol administradas através de inalador dosimetrado com espaçador em crianças com asma aguda moderada ou grave não resultou em menor taxa de internação, menor tempo de permanência na sala de emergência ou melhora em outros desfechos de eficácia em comparação com o regime de dosagens até recentemente proposto pelo GINA. Os dois regimes de dosagens mostraram perfis de segurança semelhantes / INTRODUCTION: The ideal dosing of albuterol via metered-dose inhalers for acute childhood asthma is not well established. This study aimed to compare two dosing regimens of albuterol via metered-dose inhaler with spacer in children with moderate to severe asthma attacks. The hypothesis of this study were: I. Patients with moderate to severe asthma attacks would benefit from higher doses of albuterol than those recommended until recently by the Global Initiative for Asthma (GINA). II. Higher doses of albuterol are safe for children two years of age and older. OBJECTIVES: I. To compare the efficacy (mainly length of stay in the emergency room and admission rates) of higher doses of albuterol with those recommended until recently by the GINA. II. To assess the safety of different doses of albuterol by monitoring for possible side effects and measuring drug plasma levels. METHODS: This was a prospective, randomized, controlled, double-blind study conducted in emergency rooms of the three participating centers in the city of São Paulo. We included patients with 2-17 years old with moderate to severe acute asthma (Pediatric Respiratory Assessment Measure, PRAM, score >= 5). Dosages of albuterol via metered-dose inhaler with spacer administered during the first hour included: 6 (up to 25 kg) or 12 puffs ( > 25 kg) in the control group and 9 (up to 15 kg), 12 ( > 15 to 20 kg), 15 ( > 20 to 25 kg) or 18 puffs ( > 25 kg) in the study group. Each puff contained 100 mcg of albuterol. All patients received corticosteroids and ipratropium bromide. Primary outcomes were the length of stay in the emergency room for non-admitted patients, and rate of admission. Secondary outcomes included forced expiratory volume in one second (FEV1) changes following one hour, PRAM score, pulse oximetry and respiratory rate changes following one hour and at the final time (discharge or admission, maximum four hours) and the need for additional therapies after the first hour. Safety outcomes included changes in serum potassium, glucose, bicarbonate and pH at the final time in comparison with the initial time, as well as electrocardiogram abnormalities, plasma albuterol levels, heart rate, and tremors (the last two after one hour and at the final time). RESULTS: We included 119 patients with similar baseline conditions, and no significant differences were observed between groups in the length of stay in the emergency room (p=0.55) or admission rates (p=0.48). No significant differences were observed between groups in FEV1 changes after one hour, and PRAM score, pulse oximetry and respiratory rate changes after one hour and at the final time. There were no significant differences between groups in additional therapies administered after the first hour. No significant differences were observed in safety outcomes between groups. CONCLUSIONS: Higher dosage regimens of albuterol via metered-dose inhaler with spacer for children with moderate to severe acute asthma did not result in lower admission rate, shorter length of stay in the emergency room or improvement in other efficacy outcomes in comparison with those recommended until recently by the GINA. Both dosage regimens showed similar safety profile

INTRODUÇÃO: A dosagem ideal de salbutamol através de inaladores dosimetrados para o tratamento da asma aguda na infância não está bem estabelecida. Este estudo visou comparar dois regimes de dosagem de salbutamol via inalador dosimetrado com espaçador em crianças com crises moderadas ou graves de asma. As hipóteses deste estudo foram: I. Pacientes em vigência de crises de sibilância moderadas ou graves necessitam doses de salbutamol maiores que as até recentemente recomendadas pelo Global Initiative for Asthma (GINA). II. Doses maiores de salbutamol são seguras para crianças com idade igual ou superior a dois anos de idade. OBJETIVOS: I. Avaliar a eficácia (principalmente tempo de permanência na sala de emergência e taxas de internação hospitalar) de um regime de doses maiores de salbutamol em comparação com as até recentemente recomendadas pelo GINA. II. Verificar a segurança destas dosagens de salbutamol através do monitoramento de possíveis efeitos colaterais e dos níveis plasmáticos desta droga. MÉTODOS: Este foi um estudo prospectivo, randomizado, duplo-cego e controlado realizado em salas de emergência de três centros na cidade de São Paulo. Foram incluídos pacientes com 2-17 anos de idade com asma aguda moderada a grave (escore PRAM, Pediatric Respiratory Assessment Measure, >= 5). As dosagens de salbutamol via inalador dosimetrado com espaçador administradas durante a primeira hora foram: 6 (até 25 kg) ou 12 jatos ( > 25 kg) no grupo controle e 9 (até 15 kg), 12 ( > 15 a 20 kg), 15 ( > 20 a 25 kg) ou 18 jatos ( > 25 kg) no grupo estudo. Cada jato continha 100 mcg de salbutamol. Os pacientes dos dois grupos receberam corticosteroides e brometo de ipratrópio. Os desfechos principais do estudo foram o tempo de permanência na sala de emergência para os pacientes não internados e a necessidade ou não de internação hospitalar. Os desfechos secundários foram: mudança no volume expiratório forçado no primeiro segundo (VEF1) após uma hora, mudanças no escore PRAM, na oximetria de pulso e na frequência respiratória após uma hora e no tempo final (momento da alta ou internação hospitalar, máximo de quatro horas) e a necessidade de tratamentos adicionais após a primeira hora. Os desfechos de segurança incluíram mudanças nos níveis séricos de potássio, glicose, bicarbonato e pH no tempo final em relação ao tempo inicial, bem como possíveis anormalidades no eletrocardiograma, níveis plasmáticos de salbutamol, mudanças na frequência cardíaca e presença ou ausência de tremores, os dois últimos após uma hora e no tempo final. RESULTADOS: Foram incluídos 119 pacientes com condições basais semelhantes e não foram observadas diferenças significativas entre os grupos no tempo de permanência na sala de emergência (p=0.55) ou nas taxas de internação hospitalar (p=0.48). Não foram observadas diferenças significativas entre os grupos nas mudanças de VEF1 após uma hora, nas mudanças de escore PRAM, na oximetria de pulso e na frequência respiratória após uma hora e no tempo final. Não houve diferenças significativas entre os grupos na necessidade de tratamentos adicionais administrados após a primeira hora. Não foram observadas diferenças significativas nos desfechos de segurança entre os grupos. CONCLUSÕES: O uso de doses maiores de salbutamol administradas através de inalador dosimetrado com espaçador em crianças com asma aguda moderada ou grave não resultou em menor taxa de internação, menor tempo de permanência na sala de emergência ou melhora em outros desfechos de eficácia em comparação com o regime de dosagens até recentemente proposto pelo GINA. Os dois regimes de dosagens mostraram perfis de segurança semelhantes / INTRODUCTION: The ideal dosing of albuterol via metered-dose inhalers for acute childhood asthma is not well established. This study aimed to compare two dosing regimens of albuterol via metered-dose inhaler with spacer in children with moderate to severe asthma attacks. The hypothesis of this study were: I. Patients with moderate to severe asthma attacks would benefit from higher doses of albuterol than those recommended until recently by the Global Initiative for Asthma (GINA). II. Higher doses of albuterol are safe for children two years of age and older. OBJECTIVES: I. To compare the efficacy (mainly length of stay in the emergency room and admission rates) of higher doses of albuterol with those recommended until recently by the GINA. II. To assess the safety of different doses of albuterol by monitoring for possible side effects and measuring drug plasma levels. METHODS: This was a prospective, randomized, controlled, double-blind study conducted in emergency rooms of the three participating centers in the city of São Paulo. We included patients with 2-17 years old with moderate to severe acute asthma (Pediatric Respiratory Assessment Measure, PRAM, score >= 5). Dosages of albuterol via metered-dose inhaler with spacer administered during the first hour included: 6 (up to 25 kg) or 12 puffs ( > 25 kg) in the control group and 9 (up to 15 kg), 12 ( > 15 to 20 kg), 15 ( > 20 to 25 kg) or 18 puffs ( > 25 kg) in the study group. Each puff contained 100 mcg of albuterol. All patients received corticosteroids and ipratropium bromide. Primary outcomes were the length of stay in the emergency room for non-admitted patients, and rate of admission. Secondary outcomes included forced expiratory volume in one second (FEV1) changes following one hour, PRAM score, pulse oximetry and respiratory rate changes following one hour and at the final time (discharge or admission, maximum four hours) and the need for additional therapies after the first hour. Safety outcomes included changes in serum potassium, glucose, bicarbonate and pH at the final time in comparison with the initial time, as well as electrocardiogram abnormalities, plasma albuterol levels, heart rate, and tremors (the last two after one hour and at the final time). RESULTS: We included 119 patients with similar baseline conditions, and no significant differences were observed between groups in the length of stay in the emergency room (p=0.55) or admission rates (p=0.48). No significant differences were observed between groups in FEV1 changes after one hour, and PRAM score, pulse oximetry and respiratory rate changes after one hour and at the final time. There were no significant differences between groups in additional therapies administered after the first hour. No significant differences were observed in safety outcomes between groups. CONCLUSIONS: Higher dosage regimens of albuterol via metered-dose inhaler with spacer for children with moderate to severe acute asthma did not result in lower admission rate, shorter length of stay in the emergency room or improvement in other efficacy outcomes in comparison with those recommended until recently by the GINA. Both dosage regimens showed similar safety profile

BACKGROUND: Aerosol therapy using albuterol is one of the most prescribed asthma treatments. The most frequently used methods of aerosol delivery are pneumatic jet nebulizer (JN), pressurized metered-dose inhaler (pMDI), and breath-actuated nebulizer (BAN). Choosing among these devices is usually not based on thorough comparison of efficiency or cost. We compare the efficiency of these three devices using a spontaneously breathing adult model. METHODS: We connected each aerosol generator—JN, BAN, or pMDI with a valved holding chamber (VHC)—to the face of an adult teaching manikin. Below the bifurcation, an elbow adaptor was connected to a corrugated tube and was angled to be at a lower level than the collecting filter to prevent droplets from dripping directly into the collecting filter. From the collecting filter, another corrugated tube was connected to a prevention filter, which was then connected to an adult breathing simulator. Spontaneous breathing parameters were VT 450 mL, RR 20/min, and I: E ratio 1:2. First, we compared JN, BAN (2.5 mg/3 mL), and pMDI (4 puffs); second, we compared JN and BAN 2.5 mg/0.5 mL plus 0.5 mL normal saline. Data were analyzed using spectrophotometry (276 nm). One-way ANOVA and independent sample t-tests were used (p<0.05). RESULTS: There were no differences in inhaled mass percentage (p=0.172) JN, BAN, and pMDI in the first experiment. Treatment time with BAN was significantly longer (p=0.0001) than with JN or pMDI. In the second experiment, BAN delivered more medication (p=0.004) than jet nebulizer. Treatment time was significantly less with JN (p=0.010). There was no difference in residual volume among JN and BAN in both experiment (p=0.765, p=0.115). CONCLUSIONS: All the devices that were compared using a 3 ml or 4 pMDI puffs delivered comparable amount of medication with no significant difference. However, BAN using 1ml fill volume delivers more drug compared to JN. Additionally, treatment time was longest with BAN. Even with reduction of its filling volume, BAN delivers a higher amount of medication to that of pMDI but was not statistically significant.

Diss. (sammanfattning) Linköping : Univ., 2003. / Härtill 4 uppsatser.

Dissertação (mestrado) - Pontifícia Universidade Católica do Paraná, Curitiba, 2005 / Inclui bibliografia / Crianças e adolescentes em crise aguda de asma devem ser tratadas com broncodilatadores ?2-agonistas através de aerossolterapia. Existe uma ampla gama de dispositivos que geram aerossóis para o uso destes medicamentos. O objetivo deste estudo foi: 1) veri

Interactions of Asthma Drugs with Artificial Saliva and Mucus. Modeling pulmonary particulate transport requires related biofluid physicochemical properties. Aims included measuring the effects of common aerosol drugs on artificial saliva and diffusivities of asthma medications in mucus. Artificial saliva solutions doped with asthma medications were characterized by pH, interfacial tension, and rheology. To measure diffusion, drug concentration was monitored by time-dependent FTIR spectra, and diffusivity obtained using Fick¡¦s second law. Measured theophylline and albuterol diffusivities were ca. 10-6 cm2/s. Surface Modification of Polymer Films with Light-Emitting Chemicals. To develop a polymer film system that changed color in response to radiation, acid groups of poly(ethylene-co-acrylic acid) were used to attach two light-emitting polymers: 4„S-(octyloxy)-4-biphenylcarboxylic acid and 2,7-bis(bromomethyl)-9,9-dihexyl-9Hluorene. Each reaction step was confirmed using static contact angle goniometry, FTIR spectroscopy, and X-ray photoelectron spectroscopy. UV-Vis and fluorescence spectroscopy measured the absorption spectra. Modified films were irradiated (ƒÜ=254 nm) and produced blue emissions.

No description available.

Introduction: Several problems arise when HMEs are used while giving aerosolized medication including increased airway resistance (Raw) or the need to open the ventilator circuit. Recently, heat and moisture exchangers designed to allow aerosol delivery (HME-AD) have been developed to solve this problem, but no tests have been performed to confirm their effectiveness. The purpose of this study is to evaluate the effect of HME-ADs on aerosol deposition and Raw. Methods: An in-vitro lung model consisting of an 8.0 mm ID endotracheal tube (ETT) connected to a standard ventilator circuit and ventilator was connected to a rubber test lung via cascade humidifier set to deliver 37˚C and 100% relative humidity. The ventilator settings were as follows: Vt 450 ml, RR 20/min, PIF 50 L/min, PEEP 5 cm H2O, and I:E ratio 1:2. HME-ADs used in this study include Circuvent HME/HCH bypass (Smiths-Medical, Keene, NH), Gibeck Humid-Flo HME (Hudson RCI, Arlington Heights, IL), and Airlife BHME (Carefusion, San Diego, CA). As a control, albuterol sulfate (2.5 mg/3mL) was delivered with a vibrating mesh nebulizer (Aeroneb Solo, Aerogen Inc) placed at the wye without any HME-AD in the circuit. Then, the aerosol and HME configurations of each HME-AD were tested by measuring pre-post Raw and aerosol deposition at the end of each run. Each condition was repeated in triplicate (n=3). Aerosol deposition between the aerosol and HME configurations of each HME-AD was compared with a series of student t-tests. Then, differences both in aerosol deposition and in airway resistance among the HME-ADs were analyzed using one-way analysis of variance (ANOVA). Significance was determined as p<0.05. Results: Raw increased after each albuterol treatment with every HME-AD. In the aerosol configuration, the Circuvent and Humid-Flo delivered significantly less aerosol compared to the control (p=.004 and p=.002, respectively), while there was no significant difference on aerosol delivery between the Airlife and the control (p=.084). The Airlife gave the highest aerosol deposition which was not significantly different than control (p=.084). When aerosol delivery between the HME and aerosol configurations in each HME-AD was compared, aerosol deposition with the Humid-Flo was not significantly different (p=.078) but both the Airlife and the Circuvent showed a statistically significant reduction in aerosol deposition with the HME configuration (p=.002 and p=.005). Conclusions: Aerosol delivery and Raw with each HME-AD differ in simulated mechanically ventilated patients. Further studies are needed to determine the effectiveness of these devices over time and with different aerosol generating devices.