The phase-out of chlorofluorocarbons (CFCs) has resulted in an expanding new area of research in alternative ozone friendly propellants, for example hydrofluoroalkanes (HFAs). The HFA solvent system is unique in that many CFC soluble compounds behave differently in the HFA alternatives, such as HFA-134a and HFA-227. The reason for the difference in solubility is not fully recognized. This work investigates the solubility of 22 compounds in HFA-227 with the addition of ethanol as a cosolvent. The physical properties of both solute and solvent were investigated in order to determine the effects on solubility. The solubilities of 5 compounds in HFA-134a were also investigated. A thermodynamic approach was utilized in order to look at the enthalpic and entropic effects on solubility in the propellant. Due to the high vapor pressure of propellants, a liquid model was utilized, owing to its ease of use in characterizing solubility. The correlation between the liquid model 2H,3H-decafluoropentane (DFP) and the propellants HFA-134a and HFA-227 was examined.The solubilities in HFA-227 with ethanol ranged from 0.001 to 3.282 %w/w, where the solubilities always increase when ethanol was added. The experimental solubilities were compared to calculated values obtained from ideal solubility and regular solution theory models. A clear correlation with the ideal solubility (melting point) combined with an intercept term and two physical properties was noted. A regression approach was also used to predict the activity coefficient in HFA-227 with 0 - 20% ethanol. These equations were combined with the extended ideal solubility equation, creating a useful predictive equation with AAE values ranging from 0.32 to 0.36, or factor errors of 2.09 to 2.29. The equations shown in this work are useful for the prediction of solute solubility in HFA-227/ethanol mixtures.Results in the liquid model DFP with 0 - 20% ethanol show that a regression equation results in a useful predictive equation for the solubilities in both HFA-134/ethanol and HFA-227/ethanol systems, where the AAE values ranged from 0.3 to 0.56, or factor errors of 2.0 to 3.6.The solubilities of a series of chlorobenzene compounds along with a group of hydrogen donating and/or accepting compounds was examined in HFA-134a. The entropic effects appear to be the limiting factor in the solubility of these compounds. The compounds capable of hydrogen accepting and donating exhibited negative enthalpy of mixing values when placed in HFA-134a, a stark contrast to the values obtained for the chlorobenzenes. This suggests HFA-134a is able to strongly interact with solutes capable of donating or accepting hydrogen.

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Dry powder inhalers (DPIs) are a common therapeutic modality for lung diseases such as asthma, but they are also used to treat systemic diseases such as diabetes. Advantages of DPIs include their portable design and low manufacturing costs. Another advantage of DPIs is their breath activation, which makes them popular among patients. In a passive DPI drug is only released when the patient inhales. When the patient inhales, air flows through the device. The flow of air entrains a dry powder formulation inside the device and carries it to the lung. Currently, no DPI exists which can deliver drug independent of the patient to the desired target site in the lung. This is because drug release depends on the patient’s inhalation manoeuvre. To maximize the effect of the treatment it is necessary to optimize DPIs to achieve drug delivery that (A) is independent of the inhalation manoeuvre and (B) is targeted to the correct site in the lung. Therefore, this thesis aims to apply numerical and experimental methods to optimize DPIs systematically. First, two clinically justifiable cost functions have been developed corresponding to the DPI design objectives (A) and (B). An Eulerian-Eulerian (EE) computational fluid dynamics (CFD) approach has then been used to optimize a DPI entrainment geometry. Three different optimized entrainment geometries have been found corresponding to three different therapeutic applications. Second, the CFD approach has been validated experimentally. This is the first experimental study to validate an EE CFD approach for DPI modelling. Third, a personalized medicine approach to DPI design has been proposed. The development of this approach makes it possible to achieve the design objectives for patients with highly different lung functions. Finally, an adaptive DPI with a variable bypass element has been developed. This DPI achieves design objectives (A) and (B) for patients with highly different lung functions with a single device. In contrast to the personalized medicine approach, there is no need to select the optimal amount of bypass, since the device adapts automatically.

A recently mandated change in the use of pharmaceutical propellants spurred the development and reevaluation of aerosolized pharmaceuticals. Chlorofluorocarbon (CFC) propellants were commonly used in pressurized metered dose inhalers (MDIs), but were unfortunately linked to the depletion of the ozone layer. As such, a search for new propellants was initiated and ultimately resulted in the implementation of hydrofluoroalkane (HFA) propellants in MDIs. These HFA propellants however demonstrated significantly different properties than CFCs and necessitated a considerable amount of reformulation efforts. Not only did HFAs demonstrate different physiochemical properties, but in some cases these differences necessitated reengineering of the delivery device. Unfortunately HFA propellants are considered greenhouse gasses, albeit to a lesser degree than CFCs, so the development of alternate delivery methods has been ongoing. One delivery method that has received significant attention and resources is dry powder inhalers (DPIs). DPIs are a propellant-free alternative to aerosolized drug delivery, and demonstrate some advantages and disadvantages compared to the use of MDIs and nebulizers.In addition to the modernization of pharmaceutical agents, excipients, and delivery devices, technological advances have allowed for different and/or improved characterization of pharmaceutical aerosols. Particle size characteristics of aerosols are the primary physical measure examined and are relevant to ensure proper and reproducible drug delivery to the lung. Likewise, chemical analysis of the pharmaceutical agent is extremely important for pharmaceutical development and monitoring, including solubility determination, stability monitoring, and ultimately, dose emitted. Because many limitations exist in characterization however, and because experimental means can be costly with regard to labor and materials, prediction of aerosol performance characteristics based on formulation and device variables are valuable.Previous work predicting the performance of solution based MDIs has opened the door for improved prediction of suspension based MDI systems. Suspension aerosol prediction has been examined in the past, but additional information is now available to more appropriately model suspension MDI systems that include polydisperse drug material and emit polydisperse droplets.

Nobody can live without oxygen. What happens when you have a chronic disorder that prevents the oxygen from reaching your lungs? This condition is called asthma and affects millions of people. Symptoms might be from a wheezing to a severe asthma attack with airways obstruction. It is difficult, above all for children, to accept a condition that might unexpectedly come anytime.   The Super-air inhaler is thought as a Super Hero, the worship the child has for the Hero will make the child feel strong and he will not feel ashamed of using it when having an attack. The inhaler has also been designed to make it easy for the child to take his medicine during the day and at night time too.

Anticholinergic therapy has long been a cornerstone of management of chronic obstructive pulmonary disease (COPD) but has not been included in treatment guidelines for asthma. In September 2015, tiotropium bromide was approved for use in adults with asthma; the indication has since been expanded to children ages 6 years and older. This article discusses appropriate patient selection and dosing, and the role of tiotropium bromide in asthma management.

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BACKGROUND Inhalation therapy has proven to be the best way to control the asthma and chronic obstructive pulmonary disease symptoms. The most commonly used delivery system to control these symptoms is the metered-dose inhaler. The primary goal of this study is to demonstrate an association between incorrect inhaler use and patient age. METHODS This is a cross-sectional study, performed at Centro Médico Naval “Cirujano Mayor Santiago Távara”, in Callao, Peru, in 2014. Patients older than 18 years that used metered-dose inhalers were included. We used film recordings of patients using a metered-dose inhaler and compared their technique with the recommendations on the guidelines on the correct use of inhalers of the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). The main variables measured were age and incorrect inhaler use. The results were analyzed with the Chi squared test for bivariate analysis, and for multivariate analysis we used the Poisson regression model with robust variance. RESULTS We included 378 patients in the analysis; 167 were older than 60 years. An association was found between incorrect inhalator technique and age (p=0.014) (PR 1.19 95% CI 1.03 to 1.37). The highest prevalence of incorrect technique was found in the young adult population (88%). There was no association between the incorrect technique and the person who taught it (p=0.114). Finally, this study showed that 81.2% of the study population presented an incorrect inhalation technique. CONCLUSIONS The percentage of incorrect inhaler use, in the general population is high. Even if we found no association between an incorrect technique and the person who taught it; still, there is a high percentage of errors and it was even demonstrated that being instructed by a pulmonologist does not guarantee a correct performance of metered-dose inhaler inhalations. / INTRODUCCIÓN La terapia inhalatoria ha demostrado ser la más rápida y eficaz para el control del asma y la enfermedad pulmonar obstructiva crónica. El inhalador de dosis medida es el más usado por la población. El objetivo de este estudio es evidenciar la asociación entre la técnica inhalatoria incorrecta y la edad. MÉTODOS Estudio observacional, analítico, de corte transversal realizado en Perú durante 2014. Se incluyeron pacientes desde los 18 años que utilizaran inhalador de dosis medida. Se utilizó una lista de verificación de pasos establecidos por la Sociedad Española de Neumología y Cirugía Torácica y filmaciones para evaluar la técnica inhalatoria de los pacientes. Las variables principales fueron la edad y la mala técnica inhalatoria práctica. Para el análisis bivariado se utilizó la prueba Chi cuadrado y para el análisis multivariado regresión de Poisson con varianza robusta. RESULTADOS Se incluyeron 378 pacientes; 167 fueron mayores de 60 años. El estudio reveló que el 81,2% de la población presentó una incorrecta técnica inhalatoria. Se encontró asociación entre la edad y la técnica inhalatoria incorrecta (p=0,014) (PR 1,19 con IC 95% 1,03-1,37). El grupo etario con mayor frecuencia de técnica incorrecta fue el de adultos jóvenes (88%). CONCLUSIONES La frecuencia de uso incorrecto del inhalador en la población es alta y esta característica predomina en el grupo de adultos jóvenes. A pesar de no haber asociación entre la persona que enseña la técnica inhalatoria y el desempeño de la misma, se demostró que existe alta frecuencia de errores, incluso en aquellos pacientes instruidos por un médico especialista.