Dissertations / Theses: 'Inhalation'

1

Bayer, Andreas. "Inhalation von Stickstoffmonoxid." Diss., lmu, 2006. http://nbn-resolving.de/urn:nbn:de:bvb:19-53068.

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2

Learoyd, Tristan P. "Controlled release in inhalation." Thesis, Aston University, 2007. http://publications.aston.ac.uk/11061/.

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Inhalation has become an increasingly viable alternate route to oral dosing, with the advantage of treating local disease with minimal systemic side effects (Hickey, 1992). However, increasingly complicated medication regimens associated with the necessity of the repeated dosing of multiple agents used in treating pulmonary disease has been shown to compromise both disease management and patient convenience. In this study the viability of spray drying to introduce controlled release vectors into dry powders for inhalation was investigated. The first experimental section highlights the use of leucine in producing highly respirable spray dried powders, with in vitro respirable fractions (Fine particle fraction, FPF: F < 5µm) exceeding 80% of the total dose. The second experimental chapter introduces the biocompatible polymer chitosan (mw 190 – 310 kDa) to formulations containing leucine with findings of increased FPF with increasing leucine concentration (up to 82%) and the prolonged release of the active markers terbulataline sulfate (up to 2 hours) and beclometasone dipropionate (BDP: up to 12 hours) with increasing chitosan molecular weight. Next, the thesis details the use of a double emulsion format in delivering the active markers salbutamol sulfate and BDP at differing rates; using the polymers poly-lactide co-glycolide (PLGA 50:50 and PLGA 75:25) and/or chitosan incorporating leucine as an aerosolisation enhancer the duration of in vitro release of both agents reaching 19 days with FPF exceeding 60%. The final experimental chapter involves dual aqueous and organic closed loop spray drying to create controlled release dry powders for inhalation with in vitro sustained release exceeding 28 days and FPF surpassing 55% of total loaded dose. In conclusion, potentially highly respirable sustained release dry powders for inhalation have been produced by this research using the polymers chitosan and/or PLGA as drug release modifiers and leucine as an aerosolisation enhancer.

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3

Renfrew, C. W. "Studies in inhalation anaesthesia delivery." Thesis, Queen's University Belfast, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.273051.

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Pitchayajittipong, Chonladda. "Engineering of particles for inhalation." Thesis, University of Bath, 2008. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.501621.

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Current pharmaceutical engineering for the manufacture of binary and combined dry powder inhaler (DPI) dosage forms relies on destructive strategies such as micronisation to generate respirable drug particles. Such processes are inefficient and difficult to control to produce particles of defined quality and functionality for inhaled drug delivery, which can affect drug product performance throughout the shelf-life of the product. Furthermore, owing to current pharmaceutical manufacturing practises of combined inhalation products, these products are subject to greater variability in dose delivery of each active, which may be perpetuated as a function of product storage conditions and limit clinical efficacy of the drug product. Hence, there is a requirement of processes that may enable production of binary and combination DPI products that will allow actives to be delivered more efficiently and independently of dose variations. The aim, therefore, of this study was to develop the solution atomisation and crystallisation by sonication (SAX) process for engineering of single and combination drug particles with suitable physicochemical properties for delivery to the lungs. The SAX process consists of key stages, which include, solution atomisation to produce aerosol droplets, generation of highly supersaturated droplets by evaporation of carrier solvent from aerosol droplet, collection of droplets in a crystallisation vessel containing appropriate non-solvent and the application of ultrasonic waves to the crystallisation vessel. Atomisation of a 1.5% w/v solution of budesonide in dichloromethane resulted in particles with defined surface geometry, which were formulated in binary dry powder inhaler (DPI) formulations and assessed using the next generation impactor.

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Falcone, Pin Bruno Nicolás. "Physicochemical properties of inhalation drugs." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648175.

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6

Steiner, Thierry. "Intoxications collectives aiguës par inhalation." Bordeaux 2, 1993. http://www.theses.fr/1993BOR2M191.

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7

Kwok, Philip Chi Lip. "Electrostatics of aerosols for inhalation." Thesis, The University of Sydney, 2007. http://hdl.handle.net/2123/1934.

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Electrostatics of aerosols for inhalation is a relatively new research area. Charge properties of these particles are largely unknown but electrostatic forces have been proposed to potentially influence lung deposition. Investigation on the relationship between formulation and aerosol charging is required to understand the fundamental mechanisms. A modified electrical low pressure impactor was employed to measure the particles generated from metered dose inhalers and dry powder inhalers. This equipment provides detailed size and charge information of the aerosols. The particles were sized by impaction onto thirteen stages. The net charges in twelve of the size fractions were detected and recorded by sensitive electrometers. The drug deposits were quantified by chemical assay. The aerosol charge profiles of commercial metered dose inhalers were product-dependent, which was due to differences in the drug, formulation, and valve stem material. The calculated number of elementary charges per drug particle of size ≤ 6.06 μm ranged from zero to several ten thousands. The high charge levels on particles may have a potential effect on the deposition of the aerosol particles in the lung when inhaled. New plastic spacers marketed for use with metered dose inhalers were found to possess high surface charges on the internal walls, which was successfully removed by detergent-coating. Detergent-coated spacer had higher drug output than the new ones due to the reduced electrostatic particle deposition inside the spacer. Particles delivered from spacers carried lower inherent charges than those directly from metered dose inhalers. Those with higher charges might be susceptible to electrostatic forces inside the spacers and were thus retained. The electrostatic low pressure impactor was further modified to disperse two commercial Tubuhaler® products at 60 L/min. The DPIs showed drug-specific responses to particle charging at different RHs. The difference in hygroscopicity of the drugs may play a major role. A dual mechanistic charging model was proposed to explain the charging behaviours. The charge levels on drug particles delivered from these inhalers were sufficiently high to potentially affect deposition in the airways when inhaled. Drug-free metered dose inhalers containing HFA-134a and 227 produced highly variable charge profiles but on average the puffs were negatively charged, which was thought to be due to the electronegative fluorine atoms in the HFA molecules. The charges of both HFAs shifted towards neutrality or positive polarity with increasing water content. The spiked water might have increased the electrical conductivity and/or decreased the electronegativity of the bulk propellant solution. The number of elementary charges per droplet decreased with decreasing droplet size. This trend was probably due to the redistribution of charges amongst small droplets following electrostatic fission of a bigger droplet when the Raleigh limit was reached.

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Kwok, Philip Chi Lip. "Electrostatics of aerosols for inhalation." Faculty of Pharmacy, 2007. http://hdl.handle.net/2123/1934.

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PhD
Electrostatics of aerosols for inhalation is a relatively new research area. Charge properties of these particles are largely unknown but electrostatic forces have been proposed to potentially influence lung deposition. Investigation on the relationship between formulation and aerosol charging is required to understand the fundamental mechanisms. A modified electrical low pressure impactor was employed to measure the particles generated from metered dose inhalers and dry powder inhalers. This equipment provides detailed size and charge information of the aerosols. The particles were sized by impaction onto thirteen stages. The net charges in twelve of the size fractions were detected and recorded by sensitive electrometers. The drug deposits were quantified by chemical assay. The aerosol charge profiles of commercial metered dose inhalers were product-dependent, which was due to differences in the drug, formulation, and valve stem material. The calculated number of elementary charges per drug particle of size ≤ 6.06 μm ranged from zero to several ten thousands. The high charge levels on particles may have a potential effect on the deposition of the aerosol particles in the lung when inhaled. New plastic spacers marketed for use with metered dose inhalers were found to possess high surface charges on the internal walls, which was successfully removed by detergent-coating. Detergent-coated spacer had higher drug output than the new ones due to the reduced electrostatic particle deposition inside the spacer. Particles delivered from spacers carried lower inherent charges than those directly from metered dose inhalers. Those with higher charges might be susceptible to electrostatic forces inside the spacers and were thus retained. The electrostatic low pressure impactor was further modified to disperse two commercial Tubuhaler® products at 60 L/min. The DPIs showed drug-specific responses to particle charging at different RHs. The difference in hygroscopicity of the drugs may play a major role. A dual mechanistic charging model was proposed to explain the charging behaviours. The charge levels on drug particles delivered from these inhalers were sufficiently high to potentially affect deposition in the airways when inhaled. Drug-free metered dose inhalers containing HFA-134a and 227 produced highly variable charge profiles but on average the puffs were negatively charged, which was thought to be due to the electronegative fluorine atoms in the HFA molecules. The charges of both HFAs shifted towards neutrality or positive polarity with increasing water content. The spiked water might have increased the electrical conductivity and/or decreased the electronegativity of the bulk propellant solution. The number of elementary charges per droplet decreased with decreasing droplet size. This trend was probably due to the redistribution of charges amongst small droplets following electrostatic fission of a bigger droplet when the Raleigh limit was reached.

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9

Pritchard, Claire Halina. "Manipulation of carrier particles for inhalation." Thesis, De Montfort University, 2003. http://hdl.handle.net/2086/10676.

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The work described in this thesis was performed to investigate the effect of altering the conditions of recrystallisation for selected sugars and sugar derivatives (lactose, trehalose dihydrate and trehalose octa-acetate (TOAc» in order to assess the physical effect on the material surface. In addition to recrystallised materials, amorphous materials were also produced. The short-acting betas- agonist, salbutamol sulphate, was subsequently used to assess the relative performance of these materials as drug carriers in a dry powder inhaler (OPI). The main aim of the research was to establish whether a relationship exists between the surface characteristics of a material and the performance of the material as a drug carrier in a OP!. A fundamental part of the research involved the physiochemical characterisation of the sugars, including solubility determinations for trehalose and TOAc in a range of ethanol:water solvents. Following recrystallisation, considerable time had to be spent in order to confirm the identity of the recrystallised TOAc material, as initial analysis was not conclusive in determining that the material had remained chemically unchanged following recrystallisation. Optimisation of drying of the TOAc material following recrystallisation was also performed, and X-ray crystallography of samples of the TOAc material suggested that it exists in at least three different crystalline forms. Characterisation of the surface roughness using laser profilometry was performed before the materials (sieved to obtain a particle size range of 63 - 90 J.U1l) were blended with salbutamol sulphate (micronised to a particle size of 5 J.U1l). A multi-stage liquid impinger (MSLI) was used to quantify in vitro the performance of each material as a drug carrier from the OPI device - FlowCaps® (Hovione). Overall, the results indicated that the surface roughness values (R.) required to achieve the optimum performance as a drug carrier were in the range of 1.9 to 2.7 J.U1l. Inaddition, when considering the hydrophilic or hydrophobic nature of the sugars assessed, a trend appeared to exist. The results indicated an optimum R. in the range of 1.9 to 2.3 J.U1l for materials that exhibited hydrophobic characteristics, and a range of 2.1 to 2.7 J..UD for materials that were considered hydrophilic. Inconclusion, the results obtained indicate that a relationship between the surface characteristics of a material and its performance as a drug carrier in a OPI does exist, but that the optimum relationship is determined by a number of factors. Inaddition to the surface characteristics, the physiochemical properties of the carrier material and the active drug together with the characteristics of the chosen OPI device itself, all contribute to the relationship that determines performance.

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10

Lahoud, George. "Sevoflurane/nitrous oxide inhalation conscious sedation." Thesis, University of Leeds, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.485911.

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Concern relating to the use of chair dental general anaesthesia in the United Kingdom has been expressed for many years. In four years, 1996 to 1999 there were eight deaths in general dental practices in England of which five were children. These tragic events triggered consensus among policy makers to call for banning the use of dental general anaesthesia outside a hospital setting. Options for preventing anxiety in children who needed chair dental treatment would therefore be limited to the use of local anaesthesia combined with the use of either nitrous oxide inhalation sedation or intravenous sedation. Nitrous oxide sedation is safe but not a potent gas and when it fails, children need either intravenous sedation or general anaesthesia. A suitable alternative to intravenous sedation is desirable for children when the risks of intravenous sedation are considered unacceptable. In search of a new conscious sedation technique that may further reduce the need for general anaesthesia, particularly in children when the use of nitrous oxide sedation has failed and the use of intravenous sedation is considered unsuitable, I investigated the possible use of sevoflurane/nitrous oxide for inhalation conscious sedation (SICS) for children having chair dental treatment. The combination of a variable sub-anaesthetic concentrations of sevoflurane (0.10.3%) in conjunction with a fixed ratio of nitrous oxide and oxygen (40/60%) clinically titrated to allow dental treatment to be carried out by rendering patients more co-operative while remaining conscious and breathing spontaneously, seemed a natural way to improve the success rate of inhalation conscious sedation. The thesis describes a pilot testing of SICS and a randomised controlled study comparing SICS against nitrous oxide alone. The next step was to use balanced conscious sedation with intravenous induction and inhalational maintenance by using SICS to supplement intravenous sedative drugs for patients requiring endoscopic and/or surgical procedures aimed a~ reducing amounts of intravenous sedative drugs needed to produce a balanced sedation.with the benefit of having reduced side effects. Future work involves the development of a safe and practical system for the combination and delivery of the three substances of SICS and the testing of the use of SICS for pain relief in labour.

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11

Montgomery, F. J. "Identification and control in inhalation anaesthesia." Thesis, University of Salford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.385014.

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12

Rowland, Martin. "Electrostatic properties of particles for inhalation." Thesis, University of Bath, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.687333.

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Dry powder inhalers (DPIs) and pressurised metered dose inhalers (pMDIs) are devices used to deliver therapeutic agents to the lungs. Typically, inhaled active pharmaceutical ingredients (APIs) are electrically resistive materials and are prone to accumulating electrostatic charge. The build-up of charge on inhaled therapeutics has traditionally been viewed as a nuisance as it may result in problems such as weighing errors, agglomeration, adhesion to surfaces and poor flow. Energetic processing steps such as micronisation, blending, blister/capsule filling as well as fluidisation of the dose will result in a large number of particulate collisions which can result in charge transfer. Charge present on aerosol particles may also affect the in vivo performance by altering the inhaler delivery efficiency and promoting electrostatic precipitation within the lung. This study aimed to develop and assess repeatable and reliable methods of performing electrostatic measurements of particles for inhalation and to understand the relationship of charge with environmental relative humidity. A powder ladle was constructed to perform net charge measurements of inhalation grades of lactose and used to assess the extent of triboelectrification during low shear turbula blending. Results demonstrated the importance of the method of addition used to transfer a sample to a net charge measurement device. The electrical properties of DPI formulations were investigated using a Charge Decay Time Analyser. It was determined that both API concentration and relative humidity play an essential role in governing the extent to which a DPI formulation can become electrostatically charged and the subsequent rate of charge decay. Finally, the bipolar Next Generation Impactor (bp-NGI) was developed and assessed as a tool to measure the bipolar charge to mass ratios of therapeutic aerosol particles in order to address the unmet need of combining a bipolar charge measurement system with an industry standard aerosol particle size classifier.

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13

Mueannoom, W. "Engineering excipient-free particles for inhalation." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1425624/.

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The size of inhalable particles should be approximately between 1-5 µm to be delivered to the lower respiratory tract. However, there are some disadvantages of the powders having such a small particle size, such as the difficulty of aerosolisation due to their intrinsic cohesiveness. Generating porous particles is a way of increasing the physical size of particles to enable effective aerosolisation but remain sufficiently small to reach the lower airways. A modified Hewlett-Packard thermal inkjet printer (TIJ) and airbrush (Model 200-3, USA) were used to engineer drug solutions of the inhalable drugs salbutamol sulphate (SS) and combination particles of beclometasone dipropionate (BDP) and SS (drug-drug particles). Subsequently, L-leucine was added with the aim of improving dispersibility and aerosol performance of SS and BDP:SS particles. The results demonstrated that the spray freeze dried (SFD) particles produced from both techniques had a low density of less than 0.1 g/cm3, and were spherical and porous. The SFD SS was amorphous; whereas, the inclusion of either L-leucine or BDP in formulations produced particles exhibiting partial crystallinity. This led to an enhancement of the BDP release from the SFD BDP:SS particles in the dissolution study due to: a) the largely amorphous nature of the particles b) SS acting as a solubility enhancer and c) the high surface area of the porous structure, compared to Easyhaler® Beclometasone. The SFD particles produced by the airbrush had a smaller physical size (ca: 4-10 µm) than those from the TIJ (ca: 5-30 µm). Next generation impactor (NGI) analysis indicated that the particles sprayed from the airbrush had a smaller aerodynamic size (MMAD; 0.5-5 µm) and higher fine particle fraction (FPF) (47.8-70.8 % FPF) than those particles jetted by the TIJ. In addition, engineering the combined particles of BDP:SS using the TIJ and airbrush proved that homogeneity of the drugs was achieved due to the equality of the drugs’ deposition in each NGI stage (p > 0.05). The presence of L-leucine enhanced the dispersibility of the SFD particles as the L-leucine content was increased, due to enrichment with L-leucine on the particle’s surface, and this led to a high percentage FPF being obtained. Spray freeze-drying using the TIJ and airbrush requires only a small volume of the drug solution (approximately < 5 mL for TIJ and 5-20 mL for the airbrush), which means the potential for pulmonary formulation can be assessed early in the preformulation stage.

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14

Bates, Alister. "Mechanics of airflow in human inhalation." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/25515.

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The mechanics of airflow in the large airways during inspiration affects important physiological functions such as ventilation, olfaction, heat exchange and mass transfer. The behaviour of the airflow is important not only for healthcare applications including diagnosis, intervention planning and assessment, but for inhalation toxicology. This research aims to further the understanding of human nasal physiology through computational modelling. Specifically, the effects of transient inhalation conditions on flow dynamics and transport were characterised and the changes in flow behaviour in response to certain pathologies quantified. The key findings can be summarised as follows: Firstly, the time scales for airflow in the large airways have been identified and the initial flow patterns revealed. Three phases in the temporal behaviour of the flow were identified (flow initiation, quasi-equilibrium and decay). The duration of each phase differs depending on the quantity of interest. Flow in the nose was characterised as transitional, whilst in parts of the descending airways it is turbulent, particularly in the faster moving regions around the jets which may occur in the pharynx, larynx and at the superior end of the trachea. The bulk of the flow is biased to fill only certain regions of the airways, whilst other regions carry little flow, due to features upstream. Analysis of cross-sectional images provided by medical imaging does not necessarily provide a representative view of the area available to the flow. Various scalar species were employed to represent the fate of nanoparticles and gaseous species within the airways. Only species with high diffusion rates exhibited significant absorption at the airway walls. Airway pathologies often cause changes to the geometry of the airway. One such pathology, the goitre, was found to curve the trachea and in some cases cause constriction. Both these geometric changes were found to increase the pressure loss and energy required to drive flow through the trachea. Furthermore, the flow in pathological cases was more disturbed. High resolution simulations have been used to address these topics and the scales simulated have been analysed in terms of the smallest features possible in the flow to determine their fidelity.

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15

Cosnard, Danie. "Ingestion ou inhalation de prothèses dentaires." Nantes, 1985. http://www.theses.fr/1985NANT1438.

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Lagercrantz, Forss Louise. "Adhesive mixtures for dry powder inhalation." Thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-447786.

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When it comes to dry powder inhalation (DPI), adhesive mixtures are the most widely used formulation type. Various techniques have been developed to generate inhaled drug particles and improve the delivery efficiency of DPI formulations. For dry powder inhaler formulations (DPIs), micronized drug powders are usually mixed with lactose carriers to improve powder handling during manufacturing and powder aerosol delivery during patient use. The performance of DPI systems is strongly dependent on several formulation factors, the construction of the delivery device and the inhalation technique. There is a growing interest in DPI in new medical areas such as vaccines and antibiotics which requires further development and challenges to ensure physical and aerosolization stability of DPI. This project aims to discuss the development of inhalation therapy, the challenges during formulation processes, the mixing process and the use of excipients in pulmonary drug delivery in DPIs. Further, the project is covered by experiments based on the literature overview and performed at the Department of Pharmaceutical Biosciences at Uppsala University. Bulk density was measured on three series of adhesive mixtures with increasing amounts of fine particles. In two series, small amounts of Magnesium Stearate, 0,1% and 0,01% were added.

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Bois, Olivia. "ORDNADE BLANDNINGAR FÖR INHALATION Vilken effekt har bärarpartiklarnas partikelstorlek och ytstruktur på hur lätt läkemedlet lossnar vid inhalation?" Thesis, Umeå universitet, Institutionen för integrativ medicinsk biologi (IMB), 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-179275.

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18

Guaquiere, Juliette Segolene. "Studies of spray dried particles for inhalation." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.399330.

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19

Stank, Katharina [Verfasser]. "Oberflächenmodifizierung von Wirkstoffen zur Inhalation / Katharina Stank." Kiel : Universitätsbibliothek Kiel, 2014. http://d-nb.info/1052020305/34.

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Ashurst, Ian C. "Physicochemical characteristics of chlorofluorohydrocarbon based inhalation aerosols." Thesis, Aston University, 1985. http://publications.aston.ac.uk/12546/.

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The aim of this work was to gain a better understanding of the physiochemical factors which affect the formulation of suspension inhalation aerosols. This has been attempted by applying the principles of colloid science to aerosol formulation. Both a drug system and a model colloid system have been used. The adsorption of six nonionic and cationic surfactants onto Spherisorb has been investigated. The results were analysed by calculating the area occupied by one adsorbed molecule at the surface and by comparing these values for each surfactant. The amount of each surfactant adsorbed was correlated with the number of sites on that surfactant molecule which could interact with the surface. The stability of suspensions, produced by both the model colloid Spherisorb, and by the drug isoprenaline sulphate, after adsorption of the surfactants, has been assessed by measuring settling times and rising times. The most stable suspensions were found to be those which had the greatest amounts of long chain fatty acid surfactant adsorbed on their surface. A comparison was made between the effective stabilising properties of Span 85 and oleic acid on various drug suspensions. It was found that Span 85 gave the most stable suspensions. Inhalation aerosol suspensions of isoprenaline sulphate were manufactured using the same surfactants used in the adsorption and suspension stability studies and were analysed by measuring the particle size distributions of the suspension and the emitted doses. The results were found to correlate with the adsorption and suspension stability studies and it was concluded that a deflocculated suspension was preferable to a flocculated suspension in inhalation aerosols provided that the drug density was less than the propellant density. The application of this work to preformulation studies was also discussed.

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Sherman, Jay Michael. "Inhalation exposure system for diesel exhaust particulates." Morgantown, W. Va. : [West Virginia University Libraries], 2003. http://etd.wvu.edu/templates/showETD.cfm?recnum=2844.

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Thesis (M.S.)--West Virginia University, 2003.
Title from document title page. Document formatted into pages; contains vii, 112 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 109-112).

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Wong, Jennifer. "Electrostatic Charging in Pharmaceutical Aerosols for Inhalation." Thesis, The University of Sydney, 2015. http://hdl.handle.net/2123/14273.

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While electrostatic effects are well known and can be observed all around us, it remains among the most poorly understood areas of physics. Pharmaceutical aerosols delivered by dry powder inhalers (DPIs) are known to carry bipolar charges that may influence lung deposition. Although the relationship between the magnitude and polarity of charges on total and regional lung deposition in human subjects is unclear, an important step towards understanding this relationship requires the accurate measurement of pharmaceutical aerosol charges. Hence, this thesis is focused on characterising electrostatic charge in pharmaceutical powder aerosols. Instruments such as the Electrical Low Pressure Impactor (ELPI™) and Bipolar Charge Analyzer (BOLAR™) were utilised to simultaneously measure charge and mass distributions of inhalable products. The first study examined the differences in net charge between amorphous and crystalline salbutamol sulfate (SS) using the ELPI™. Subsequent studies investigated bipolar charges using the BOLAR™. The capability of the BOLAR™ to characterise charge bipolarity and mass distributions was evaluated using spray-dried mannitol powder. Additionally, bipolar charges from commercial products such as Bricanyl® and Pulmicort® Turbuhalers® were characterised. The final study investigated the influence of modifying the design and material of Aerolizer® inhaler on bipolar charging of spray-dried mannitol powder. To this end, the findings in this thesis have provided insight into the effects of crystallinity and inhaler design on formulation electrostatic properties which could facilitate advances that may enhance pulmonary drug delivery in the near future.

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Alaboud, S. "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." Thesis, University of Bradford, 2011. http://hdl.handle.net/10454/5686.

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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.

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Poonai, Naveen. "Carbon dioxide inhalation challenges in multiple chemical sensitivity." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape8/PQDD_0003/MQ46116.pdf.

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Anton, Segarra Rebeca. "Concept for motivating toddlers to accept inhalation therapy." Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for produktdesign, 2013. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-20988.

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This master thesis is conducted at the Institute of Product Design at NTNU. The subject of the assignment is “Concept for motivating toddlers to accept inhalation therapy”. The project aims at developing a concept for motivating hospitalized toddlers (2-3 years old) to accept inhalation therapy. The first part of the project was an investigation process to understand the situation: the disease, the children’s behaviour at 2-3 years age, the hospital environment, the treatment, etc. Secondly I started to develop some ideas that led me to the final concept. After that, having the general concept, the next step was to develop it: the concept, materials, shapes, name for the toy... In addition I had to keep in mind all the details of the interaction process between the treatment, the target and the project. Once I had the concept developed was time to go further in all the key aspects such as production, dimensions, pieces’ design, electronic components, maintenance and final results. In conclusion, BRUCE is a toy developed after investigation, detailing and interaction design work. It consists on a toy to improve children’s experience of the treatment. Concretely the goal is to engage children between 2 and 3 years with respiratory diseases, while they are taking the medication and entertain them in an active level. Making the kids part of the treatment and making the treatment meaningful for them.

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Monroe, Margaret Delia. "Citric acid inhalation cough challenge: Establishing normative data." Thesis, University of Canterbury. Communication Disorders, 2010. http://hdl.handle.net/10092/4149.

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One of the most elusive challenges in the diagnosis and treatment of dysphagia is the reliable identification of silent aspiration (aspiration in the absence of cough). The citric acid inhalation cough challenge offers potential for aiding in identification of silent aspiration; however clinical application of this technique is currently problematic due to an absence of normative data. Therefore, this study aimed to establish a normative data set for the Citric- Acid Inhalation Cough Challenge, as administered with facemask method. 80 healthy subjects will participate in this study, constituting 2 age groups: above and below 60 years, with equal gender representation. On 3 separate trials, they will be asked to passively inhale, via a facemask, nebulised citric acid of concentrations ranging from 08M to 2.6M with placebo interspersed. ‘Natural cough thresholds’ (NCT) and ‘Suppressed Cough Thresholds’ (SCT) will be reached when subjects cough on at least 2 out of 3 trials. The majority (92.5%) of participants reached Natural Cough Threshold by 0.8M, with 68% demonstrating Suppressed Cough Threshold also at this concentration. There were no significant differences found between males and females (p<0.05) for either NCT (p=0.9885) or SCT (p=0.44). Whilst no difference was found between youngers and elders for NCT (p=0.7254), there was a significant difference for SCT (p=0.018), with youngers better able to suppress cough. Over 90% of healthy people were found to elicit cough at 0.8M, inferring that this level would be an adequate guide for use by clinicians testing for presence/absence of cough.

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Hickey, A. J. "Pharmaceutical inhalation aerosols : their delivery and therapeutic applications." Thesis, Aston University, 2002. http://publications.aston.ac.uk/21776/.

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Chen, Chi. "Engineering of inhalation aerosols combining theophylline and budesonide." Thesis, University of Bradford, 2014. http://hdl.handle.net/10454/14072.

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In asthma therapy, the use of theophylline to prevent bronchial spasm and glucocorticoids to decrease inflammation is widely indicated. Apart from the acute asthma attack oral theophylline is treated for chronic therapy in order to minimize inflammation and to enhance the efficiency of corticosteroids and recover steroids’ anti-inflammatory actions in COPD treatment. The preferred application route for respiratory disease treatment is by inhalation, such as dry powder inhalers (DPI) being the delivery systems of first choice. As shown recently, there is an advantageous effect if the drugs are given simultaneously which is caused by a synergistic effect at the same target cell in the lung epithelia. Therefore, it seems rational to combine both substances in one particle. This type of particle has the advantage over a combination product containing both drugs in a physical mixture which occurs rather randomly deposition leading to API segregation and non-dose-uniformity. Dry powder inhalers (DPIs) is a type of therapeutic pharmaceutical formulations usually present in the solid form. Due to the nature of the solid-state, an understanding of chemical and physical properties must be established for acquiring optimum performance of the active pharmaceutical ingredients (APIs). In recent year, generation of DPIs is a destructive procedure to meet the micron size. Such processes are inefficient and difficult to control. Moreover, according to current researches on combination APIs formulation, this type of DPIs performed a greater variability in does delivery of each active, leading to poor bioavailability and limit clinical efficient. This result suggest that combination formulations require advanced quality and functionality of particles with suitable physicochemical properties. Hence, in order to production of binary and combination DPIs products, the aim of this study was to develop the spray drying and ultrasonic process for engineering of combination drug particles that will be delivered more efficiently and independently of dose variations to the lung. Microparticles were produced by spray drying or/and ultrasonic technique. The processing parameters and addition of excipients (polymers) were optimized using a full factorial design such that microparticles were produced in a narrow size range suitable for inhalation. Employing excipients resulted in high saturation environment leading to minimized sphere particles when compared to conventional solvent. Solid state characterization of microparticles using powder x-ray diffraction and differential scanning calorimetry indicated that the particles contained crystalline but no cocrystal. The combination particles comparable to or better than micronized drug when formulated as a powder blended with lactose. It was concluded that the use of HPMC enhanced crystallinity suitable for inhalation; and combination particles improved uniform distribution on the stage of NGI.

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Maire, Bruno. "Les pneumopathies d'aspiration graves : a propos de 41 observations." Nancy 1, 1988. http://www.theses.fr/1988NAN11003.

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Patel, Neha. "Spray drying of pharmaceuticals for controlled release pulmonary drug delivery." Thesis, University of Bath, 2000. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323589.

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Isiguzo, O. F. "Proficiency at using the metered dose inhaler among patients attending the Witpoort Hospital Outpatient Clinic." Thesis, University of Limpopo (Medunsa Campus), 2011. http://hdl.handle.net/10386/451.

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Thesis (M Med (Family Medicine))--University of Limpopo (Medunsa Campus), 2011.
AIM AND OBJECTIVE: To determine metered dose inhaler usage technique among asthmatic patients attending outpatient clinic and assess relationship between proficiency and specific factors for efficient or non-efficient usage. DESIGN: A cross-sectional study was conducted in outpatient clinic; the inhalation technique was assessed in six steps. SETTING: outpatient clinic of Witpoort hospital, Limpopo province, South Africa. RESULT: Total of 102 patients (32 male and 70 female) was assessed with age ranging from 10 to 77(mean 44) between September to November 2008. Only three (2.9%) of patients could perform all six steps correctly. Percentage of patients performing each step correctly were: 20.6% , 65.7%, 4.9%, 4.9% and 1% got none of the step, one step, two steps, three steps, and four steps correctly respectively. None got up to five steps correctly. The 2.9% that got all six steps correctly were taught by a doctor and had asthma duration of greater than five year. CONCLUSION: This study shows a high level of incorrect usage of metered dose inhaler among asthmatic patient attending witpoort hospital. Sex (gender), age and educational level did not play a role in proficiency of inhaler use.

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Magwentshu, Zolelwa Temperance. "Knowledge and practice on the use of metered dose inhalers by asthmatic patients seen at a Private General Practice in the Vhembe District, Limpopo Province." Thesis, University of Limpopo (Medunsa Campus), 2010. http://hdl.handle.net/10386/508.

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Thesis M.Med.(Family Medicine))--University of Limpopo (Medunsa Campus), 2010.
Background Asthma mortality in many countries is reported to be falling but the morbidity remains unacceptably high. One of the reasons for the latter is the reluctance to, and the inappropriate use of MDIs by patients resulting in inadequate dosing of medication and therefore poor asthma control. For family physicians to appropriately manage their asthmatic patients, they need to understand the patients’ knowledge and practice on the use of MDIs. Aim The aim of the study was to determine the knowledge and practice of asthmatic patients seen in a private general practice on the use of MDIs. Methodology A descriptive cross-sectional study was undertaken with fifty randomly selected participants. A structured questionnaire was used for data collection and data analysis was done using Microsoft Excel spreadsheet and SPSS version 17 software. Results Sixty percent (60%, n=30) of the participants were females and forty percent (40%, n=20) were males. The majority of the participants eighty two percent (82%, n=41) had asthma for more than five years. All the participants used MDIs. Ninety four percent (94%, n=47) used Asthavent® and 88% Budeflam®. Ninety four percent knew that Asthavent® was a reliever and only 20% knew that Budeflam® was a preventer. Conversely, forty percent (40%, n=20) thought that Budeflam® was a reliever. The majority of the participants were unable to correctly demonstrate the main steps in the practical use of the MDI. Conclusion The correct use of MDI was found to be poor for most participants. The majority of the participants lacked knowledge and skill for effective use of the MDI. The findings from this study provide reasons for family physicians to continuously educate their patients on the correct use of the MDI.

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Kim, Seong Woong. "Beeinflussung der zerebralen Mikrozirkulation durch Inhalation von Stickstoffmonoxid(NO)." Diss., lmu, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-95500.

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34

Bagherisadeghi, Golshan. "Real life dose emission characterization using patient inhalation profiles." Thesis, University of Huddersfield, 2016. http://eprints.hud.ac.uk/id/eprint/30322/.

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The aerodynamic characteristics of the dose emitted from dry powder inhalers (DPIs) varies from patient to patient depending on their peak inhalation flow (PIF) and may also be affected by other factors such as the inhaled volume (Vin) and the initial acceleration of the inhalation manoeuvre (ACIM). Compendial methods for the in-vitro determination of the dose emitted from inhalers recommend using a vacuum pump to simulate an inhalation but this is not representative of that made by a patient. In this study a new in-vitro methodology has been developed by adapting a mixing inlet with the Andersen Cascade Impactor (ACI) to use COPD patient inhalation profiles in place of a vacuum pump. The aim was to investigate the effect of inhalation manoeuvre parameters (PIF, Vin and ACIM) on the dose emission performance of both Symbicort® Turbuhaler® and DuoResp® Spiromax®. The medium (200 μg/6 μg budesonide[BUD]/formoterol[FORM]) and high strength (400 μg/12 μg BUD/FORM) products have been used. In the first part of this thesis a comparison has been made between the Alberta Idealised Throat (AIT) and the traditional USP Induction Port (IP) using standard in-vitro compendial methodology. The medium strength version of the Symbicort® Turbuhaler® was used. The results show that the AIT captured more drug compared to the USP IP throat (p<0.05). Regardless of the inhalation volume, no significant change was observed for the FPD at 28.3 L/min between the two throats, although there was a significant difference in the FPD when the flow was increased to 60 L/min (p<0.05). In contrast to an inhalation flow of 28.3 L/min, at 60 L/min the MMAD reduced significantly (p<0.05). No significant change was observed for TED at both inhalation flows while changing the size of the throats regardless of the inhalation volume. In the second and the last but major part, the performance of the Symbicort® Turbuhaler® and DuoResp® Spiromax® was evaluated using the medium and high strength products. The results of both inhalers indicate the importance of PIF on the dose emission characteristics as it increased from <30 to >60 L/min. As a result, both FPD and TED increased and MMAD decreased significantly (p<0.05). The Vin and ACIM showed different effects on the medium and high strength of both inhalers. Generally, Vin had a small effect on both FPD and TED which increased and no change was observed with MMAD. The ACIM also had a small impact on FPD, TED and MMAD for Symbicort® Turbuhaler® and only FPD and MMAD for DuoResp® Spiromax®. The results highlights the potential of this methodology to characterise the dose a patient receive during real life use by using these inhalation profiles in place of the inhalation provided by a vacuum pump. Overall, PIF was the dominant inhalation manoeuver parameter for the dose emission from the Symbicort® Turbuhaler® and DuoResp® Spiromax®.

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Braithwaite, M., Vuuren SF Van, and AM Viljoen. "Validation of smoke inhalation therapy to treat microbial infections." Elsevier, 2008. http://encore.tut.ac.za/iii/cpro/DigitalItemViewPage.external?sp=1000386.

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Aim of the study: In traditional healing, the burning of selected indigenous medicinal plants and the inhalation of the liberated smoke are widely accepted and a practiced route of administration. This study elucidated the rationale behind this commonly practiced treatment by examining the antimicrobial activity for five indigenous South African medicinal plants commonly administered through inhalation (Artemisia afra, Heteropyxis natalensis, Myrothamnus flabellifolius, Pellaea calomelanos and Tarchonanthus camphoratus). Material and Methods: An apparatus was designed to simulate the burning process that occurs in a traditional setting and the smoke fraction was captured for analysis and bioassay. Methanol and acetone extracts as well as the essential oil (for the aromatic species) were prepared and assayed in parallel with the smoke fraction. Results: Antimicrobial data revealed that in most cases, the ‘smoke-extract’ obtained after burning had lower minimum inhibitory concentration (MIC) values than the corresponding solvent extracts and essential oils. The combustion, acetone and methanol extracts produced different chromatographic profiles as demonstrated for Pellaea calomelanos where several compounds noted in the smoke fraction were not present in the other extracts. Conclusion: These results suggest that the combustion process produces an ‘extract’ with superior antimicrobial activity and provides in vitro evidence for inhalation of medicinal smoke as an efficient mode of administration in traditional healing.

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Altimimi, Ahmed Shafik. "Quality of life and treatment outcome under inhalation sedation." Thesis, University of Leeds, 2016. http://etheses.whiterose.ac.uk/16230/.

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AIM: To assess the outcome of treatment and changes in quality of life (QoL) following comprehensive dental treatment using nitrous oxide inhalation sedation. METHODS: Patients attending the Sedation Unit at the Leeds Dental Institute were asked to participate in the study. Baseline questionnaires included a quality of life (QoL) assessment (COHIP-SF19) and the p-IOSN tool (indication of sedation need). Participants were followed up to evaluate the outcome of their treatment. Those who completed treatment as planned completed a second QoL assessment at least 2 weeks following their last appointment. RESULTS: In total, 97 patients were recruited (44 males and 53 females), and of these 47 completed treatment as planned with 31 completing a 2nd QoL assessment, 18 are currently undergoing treatment, and 20 were referred to GA. There was a statistically significant improvement in QoL following treatment (p value= 0.000), with the largest effect size noted in the “oral health well-being” domain. When not controlling for other factors, a change from high to low anxiety was significantly associated with high baseline QoL (B= 6.632 p value = 0.023). Changing from high to low sedation need decreased the likely need for referring to GA and not completing treatment as planned (B -1.788 p value 0.05). CONCLUSION: Rendering the child dentally fit improved QoL. Using anxiety, gender, age group or sedation need as measures could not accurately predict the treatment outcome of the child or the baseline QoL scores, when controlling for sedation need and anxiety.

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Depreter, Flore. "Development of dry powder formulations of proteins for inhalation." Doctoral thesis, Universite Libre de Bruxelles, 2012. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209719.

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A number of therapeutic proteins are used for long in clinical practice. These include for example insulin, calcitonine, growth hormone, and parathyroid hormone for the treatment of various systemic disorders, as well as protein antigens in vaccine formulations. Due to the recent developments in biochemical engineering and in the comprehension of the physiopathology of many diseases, peptides and proteins are expected to become a drug class of increasing importance. Recently, novel biological drugs have for example been developed such as monoclonal antibodies, antibody fragments, soluble receptors, and receptor agonists or antagonists. These are mainly used for the treatment of auto-immune and inflammatory diseases (asthma, rheumatoid arthritis) and for the treatment of cancers. However, a major drawback of these biomolecules is the need to use parenteral administration. This is mainly due to the harsh pH conditions that proteins undergo by oral administration, leading to various physico-chemical degradations and loss of biological activity.

Pulmonary delivery of these proteins could constitute an alternative to parenteral delivery. Due to the very high surface area of the lungs, the low thickness of the alveolar epithelium and the high level of lung vascularisation, pulmonary administration can indeed provide fast systemic absorption of drugs, while avoiding hepatic first pass metabolism. On the other hand, drugs for local treatment can also be administered directly into the lung, which allows delivering high doses while limiting systemic side effects. Nevertheless, administration of drugs to the lungs requires some challenges to be taken up. It is indeed necessary to provide the drug as very small solid or liquid microparticles (1-5 µm) in order to reach the lungs. For solid microparticles, it is also needed to overcome the very high inter-particle interactions by using appropriate formulation strategies and by including deaggregation mechanisms in the inhalation device. Other issues are more specifically related to the pulmonary administration of proteins. These can indeed undergo physico-chemical degradations during processing, administration, and/or storage. Moreover, if systemic action is required, proteins will often need addition of an absorption enhancer to cross the alveolar epithelium because of their large molecular weight and hydrophilicity.

In this work, we developed formulations for pulmonary delivery of proteins using two model proteins. Insulin (5.8 kDa) was chosen as a model of small protein. It is also an application of systemic pulmonary delivery. On the other hand, an anti-IL13 monoclonal antibody fragment (54 kDa) was used as a model of larger protein. This molecule is currently in development for the treatment of asthma and provided an application for local pulmonary delivery. The formulation strategy was to produce dry powders using a combination of micronisation techniques (high speed and high pressure homogenisations), drying techniques (spray-drying, freeze-drying), and addition of lipid excipients. These lipid excipients were added as a coating around the protein particles and were expected to prevent protein degradations during processing and/or storage, essentially by avoiding contact with water. It could also improve the aerodynamic properties of the powders by modification of the surface properties of the particles and/or limitation of the capillary forces.

First, we evaluated insulin lipid-coated formulations and formulations without excipients, produced using high pressure homogenisation and spray-drying. In the case of lipid-coated formulations, a physiological lipid composition based on a mixture of cholesterol and phospholipids was used. We were able to obtain good aerodynamic features for the different formulations tested, with fine particle fractions between 46% and 63% versus 11% for raw insulin powder. These are high FPF values in comparison with those obtained for other protein formulations for inhalation currently under development, which often have an in vitro deposition of around 30%. Insulin presented a good stability in the dry state, even when no lipid coating was added.

The presence of a lipid coating of up to 30% (w/w) did not significantly improve the aerodynamic behaviour of the powders, but the coated formulations exhibited decreased residual moisture content after 3-month storage, which should be of interest for the long-term stability of the formulations.

In a second step, two of the developed insulin formulations were evaluated in a clinical study to determine whether the formulations give high deep lung deposition in vivo, and how insulin is absorbed into the systemic blood stream. This pharmaco-scintigraphic trial was performed on twelve type 1 diabetic patients using an uncoated formulation and a formulation coated with 20% (w/w) of lipids. The two formulations showed interesting features, with pharmacokinetic profiles that mimic the natural insulin secretion pattern. Bioavailability was within the ranges of two of the three dry powder insulins that have reached phase III clinical development. However, the formulation with a lipid coating exhibited a lower lung deposition in comparison with the uncoated formulation, which was not expected from the previous in vitro results. Additional in vitro experiments indicated that this lower performance was related to a decrease in the disaggregation efficiency of the powder at a sub-optimal inhalation flow-rate. An extensive training of the patients to the inhalation procedure could therefore improve the lung deposition of the coated formulation.

Finally, we developed and evaluated dry powder formulations of the anti-IL13 antibody fragment. These were produced using, successively, freeze-drying, high pressure homogenisation (HPH), and spray-drying. The influence of different types and concentrations of stabilising excipients was evaluated for each production step. Due to its more elaborated structure, the antibody fragment was found to be more sensitive than insulin to physico-chemical degradation, particularly during the HPH process, which led to different types of degradation products. These could partly be avoided by adding 50% sucrose during freeze-drying and 10% Na glycocholate or palmitic acid in the liquid phase during HPH (dispersing agents). However, the presence of a small fraction of insoluble aggregates could not be fully avoided. Further spray-drying of the suspensions in the presence of 10% Na glycocholate or palmitic acid led to the formation of a hydrophilic or hydrophobic coating around the particles, respectively. Na glycocholate was found to be particularly effective in protecting the antibody during spray-drying, which was found to be at least partly related to its ability to inhibit sucrose recrystallisation. However, the best formulation still presented a small fraction of insoluble aggregates (6%). The aerodynamic evaluation of the formulations showed FPFs that were compatible with lung deposition, with the formulation containing Na glycocholate presenting the highest FPF (42%). The formulation coated with palmitic acid presented a slightly lower FPF (35%). The aerodynamic properties of this formulation remained unchanged at a sub-optimal inspiratory flow rate, to the contrary of what was observed for the insulin formulation coated with 20% (w/w) cholesterol and phospholipids. Palmitic acid could therefore be of interest as a hydrophobic coating material, and provide long-term stability of protein drugs.

The work performed with the insulin and anti-IL13 molecules provided the proof-of-concept that it was possible to obtain dry powder protein formulations with appropriate aerodynamic properties and good overall physico-chemical stability, using simple production techniques and few selected excipients. The formulation strategy presented in this work could therefore be of interest for the future development of inhaled proteins for local or systemic applications.

Doctorat en sciences pharmaceutiques
info:eu-repo/semantics/nonPublished

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Merlos, Romain. "Development of Triazole-based Dry Powder Formulations for Inhalation." Doctoral thesis, Universite Libre de Bruxelles, 2019. https://dipot.ulb.ac.be/dspace/bitstream/2013/289299/5/these.pdf.

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Among the different pulmonary fungal infections, aspergillosis, and in particular invasive pulmonary aspergillosis (IPA), are becoming the most worrying diseases in immunocompromised patients. This is due to their high incidence and mortality. Indeed, invasive aspergillosis manifests as invasive pulmonary disease accounting for 50/60% of all cases, with a mortality of 50-90% in severely immunocompromised patients. Triazoles act by inhibiting 14-α demethylase, a fungal cytochrome P450 enzyme implicated in the synthesis of ergosterol, an essential constituent of fungal cell walls. Moreover, they interact with the same cytochrome present in large quantities in the human liver, inducing possible drug-drug interactions in IPA patients. Consequently, interactions resulting from inhibitors, inductors, or substrates of cytochromes can modify the plasmatic concentrations of triazoles or other drugs administered concomitantly. To overcome these important issues, pulmonary delivery of triazoles could be an interesting alternative to conventional routes.The aim of this work was to develop triazole-based dry powders for inhalation able to be deposited adequately in the lungs, with a release of drug and a lung retention that can optimize its pharmacological action. This work focused on two active pharmaceutical ingredients (API): itraconazole (ITZ), for which improved solubility was needed, and voriconazole (VCZ), for which slow release was required.Concerning ITZ, solid dispersions for inhalation (SDIs) comprising ITZ and mannitol were previously developed in our laboratory. The selected SDI showed interesting results in terms of improved dissolution and lung retention in vivo in mice during a pharmacokinetic study. Therefore, this SDI was tested in a murine preclinical model of IPA and showed promising results in terms of prophylaxis efficacy. One aim of this work was to continue the pharmaceutical development of this promising SDI by making a scaling-up study. These methods were intended to improve the SDI’s ecological footprint and productivity by increasing the production yield and decreasing the amount of solvents and time used in its manufacture. During the first step of this study, the obtained SDI showed interesting results obtaining similar powder characteristics (i.e. amorphous content, aerodynamic performance, and dissolution profiles) from concentrated solutions using a laboratory-scale spray-dryer B-290 (Büchi, Switzerland) before using a pilot-scale spray-dryer (GEA Niro, Denmark). Then, the upscaling was performed on the pilot spray-dryer allowing the production of SDIs with increased productivity (yield and process duration). These SDIs had similar powder characteristics than the optimized lab-scale SDIs. During the second part of this work we developed VCZ based dry powder for inhalation. The aim was to slow down the release of this highly permeable and very slightly soluble API and to prolong its lung residence. To this end, various lipidic excipients were chosen. The selection took into account the potential good pulmonary tolerance of the lipids and their hydrophobicity to evaluate their ability to slow down the VCZ release (FPFs 20-25%, slowed release up to 24h, burst effect of ± 58% of VCZ dissolved within 30min). Immediate-release SDIs were also developed to have a comparator reference for the pharmacokinetic and efficacy studies (FPFs of 40%).Then, a pharmacokinetic study in mice was performed following the pulmonary administration of one immediate-release and two sustained-release SDIs (with or without PEG excipient). With an 80-fold higher pulmonary exposure over 24 hours, the slow-release SDIs presented a real interest compared to the immediate-release SDI. Moreover, in accordance with these results, VCZ plasma exposure following the administration of the SDI with PL90-H was more than 1.5-fold higher than its pulmonary exposure (AUC0-24 of 8.70 µg.h/g in the lungs and 14.70 µg.h/mL in the plasma). The slow-release formulations presented plasma exposures at least 15 times lower than their pulmonary exposures (AUC0-24 in lung of 741.40 and 686.85 µg.h/g vs plasmatic AUC0-24 of 37.44 and 42.81 µg.h.mL, respectively with and without PEG excipient). Moreover, the presence of PEG excipient did not influence the residence time and the exposure of the VCZ within the lungs. Finally, the sustained-release SDIs administration by inhalation led to VCZ lung and plasma concentrations higher than the minimal inhibitory concentration (MIC) of VCZ against Aspergillus fumigatus (1 μg/mL) over 24 h. Finally, a murine model of IPA was developed in our lab. The immunosuppression model was fixed and performed by the intraperitoneal (IP) injection of corticosteroids to induce a neutropenia state. Then, different doses of spores (from 1.10^4 to 5.10^6 spores) were inoculated to the neutropenic mice via an endotracheal instillation and the survival rate of each group was observed. Unfortunately, the survival rate resulting from the different infections were not reproducible. Therefore, these models were not suitable to conduct the efficacy study. This underlined the link between the immunosuppressive model and the infection. Indeed, the IPA murine model should be developed according to the immune state of the animal, the Aspergillus conidia species and its concentration to be used.
Doctorat en Sciences biomédicales et pharmaceutiques (Pharmacie)
info:eu-repo/semantics/nonPublished

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39

Beck, Kayla D. "The Efficiency of Forced Inhalation in Promoting Venous Return." Ohio University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1468497752.

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Nerbrink, Ola. "Characterisation of aerosol delivery devices and their influence on deposition in humans and animals /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4753-8/.

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Ibn, Yakubu Sani. "Investigations to identify the influence of the inhalation manoeuvre on the ex-vivo dose emission and the in-vitro aerodynamic dose emission characteristics of dry powder inhalers: Studies to identify the influence of inhalation flow, inhalation volume and the number of inhalations per dose on the ex-vivo dose emission and the in-vitro aerodynamic dose emission characteristics of dry powder inhalers." Thesis, University of Bradford, 2009. http://hdl.handle.net/10454/4861.

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Currently available dry powder inhalers (DPIs) for drug delivery to the lungs require turbulent energy to generate and disperse aerosol particles in the respirable range ¿5¿m during inhalation. The patient's inspiratory effort together with the resistance inside the device creates this energy. Different inhalers provide varying degrees of resistance to inhalation flow and require different inhalation techniques for the generation and delivery of drug fine particles in respirable size range to the lungs. The aim of this research programme was to identify the influence of inhalation flow, inhalation volume and the number of inhalations per dose on the ex-vivo dose emission and the in-vitro aerodynamic dose emission characteristics of the salbutamol Accuhaler®, Easyhaler®, and Clickhaler® and the terbutaline Turbuhaler® DPIs. A high-performance liquid chromatography method for the assay of salbutamol sulphate and terbutaline sulphate in aqueous samples was modified and accordingly validated. In-vitro dose emission of the four different DPIs was measured using the pharmacopoeia method with modifications to simulate varying inhalation flows within patient and between patients. The ranges of the total emitted dose (% nominal dose) at the inhalation flow range of 10 - 60 Lmin-1, following one and two inhalations per metered dose for 2L and 4L inhaled volumes were as follows: the Accuhaler (52.64- 85.11; 61.88-85.11 and 59.23-85.11; 62.81-85.11); the Easyhaler (68.35-91.99; 79.94-91.99 and 73.83-92.51; 80.40-92.51); the Clickhaler (46.55-96.49; 51.12-96.49 and 51.18-101.39; 59.71-101.39) as well as the Turbuhaler (46.08-88.13; 51.95-88.13 and 48.05-89.22; 48.64-89.22). The results highlight that the four inhalers have flow-dependent dose emission property to a varying degree using 2L and 4 L inhaled volumes. There was no significant difference in the total emitted dose between a 2L inhaled volume and a 4L inhaled volume at each inhalation flow. Furthermore, the total emitted dose from the Easyhaler®, Clickhaler®, and Turbuhaler® was significantly (p¿0.001) greater with two inhalations than one inhalation per metered dose across the range of inhalation flow (10 ¿ 60) Lmin-1. This effect was only observed at inhalation flow less than 30 Lmin-1 with the Accuhaler®. Overall there is a significant difference in the total emitted dose. The ex-vivo dose emission of the four different DPIs has been determined using the In- Check Dial device to train twelve non-smoking healthy adult volunteers to inhale at slow (30 Lmin-1) and fast (60 L min-1) inhalation flows through the device with its dial set corresponding to each inhaler. Subsequently each volunteer inhaled at the trained inhalation flows through each active inhaler. The local ethics committee approval was obtained prior to the study and all volunteers gave signed informed consent. The results obtained demonstrate that the studied inhalers have flow-dependent dose emission, thereby enhancing confidence in the use of the In-Check Dial® to identify a patient¿s inhalation flows through a variety of DPIs. Also the total emitted dose determined by ex-vivo methodology was significantly (p¿0.05) greater with two inhalations than one inhalation per metered dose. The results of the in-vitro aerodynamic dose emission characteristics highlight that the fine particle dose (FPD) from the four studied inhalers is flow dependent. Also the minimum inhalation flow to generate the (FPD) with the appropriate characteristics for lung deposition has been identified to be 20 L min-1 for the Accuhaler®, Easyhaler® and Clickhaler®, while that for the Turbuhaler® is about 30 L min-1. Also the inhalation volume above 2L and the number of inhalations for each dose have respectively no significant (p¿0.05) influence on the FPD emitted from the four studied inhalers. The results support the present instructions to patients using these inhalers to inhale once for each dose as fast as they can.

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42

Yakubu, Sani Ibn. "Investigations to identify the influence of the inhalation manoeuvre on the ex-vivo dose emission and the in-vitro aerodynamic dose emission characteristics of dry powder inhalers : studies to identify the influence of inhalation flow, inhalation volume and the number of inhalations per dose on the ex-vivo dose emission and the in-vitro aerodynamic dose emission characteristics of dry powder inhalers." Thesis, University of Bradford, 2009. http://hdl.handle.net/10454/4861.

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Abstract:

Currently available dry powder inhalers (DPIs) for drug delivery to the lungs require turbulent energy to generate and disperse aerosol particles in the respirable range ≤5μm during inhalation. The patient's inspiratory effort together with the resistance inside the device creates this energy. Different inhalers provide varying degrees of resistance to inhalation flow and require different inhalation techniques for the generation and delivery of drug fine particles in respirable size range to the lungs. The aim of this research programme was to identify the influence of inhalation flow, inhalation volume and the number of inhalations per dose on the ex-vivo dose emission and the in-vitro aerodynamic dose emission characteristics of the salbutamol Accuhaler®, Easyhaler®, and Clickhaler® and the terbutaline Turbuhaler® DPIs. A high-performance liquid chromatography method for the assay of salbutamol sulphate and terbutaline sulphate in aqueous samples was modified and accordingly validated. In-vitro dose emission of the four different DPIs was measured using the pharmacopoeia method with modifications to simulate varying inhalation flows within patient and between patients. The ranges of the total emitted dose (% nominal dose) at the inhalation flow range of 10 - 60 Lmin-1, following one and two inhalations per metered dose for 2L and 4L inhaled volumes were as follows: the Accuhaler (52.64- 85.11; 61.88-85.11 and 59.23-85.11; 62.81-85.11); the Easyhaler (68.35-91.99; 79.94-91.99 and 73.83-92.51; 80.40-92.51); the Clickhaler (46.55-96.49; 51.12-96.49 and 51.18-101.39; 59.71-101.39) as well as the Turbuhaler (46.08-88.13; 51.95-88.13 and 48.05-89.22; 48.64-89.22). The results highlight that the four inhalers have flow-dependent dose emission property to a varying degree using 2L and 4 L inhaled volumes. There was no significant difference in the total emitted dose between a 2L inhaled volume and a 4L inhaled volume at each inhalation flow. Furthermore, the total emitted dose from the Easyhaler®, Clickhaler®, and Turbuhaler® was significantly (p≤0.001) greater with two inhalations than one inhalation per metered dose across the range of inhalation flow (10-60) Lmin-1. This effect was only observed at inhalation flow less than 30 Lmin-1 with the Accuhaler®. Overall there is a significant difference in the total emitted dose. The ex-vivo dose emission of the four different DPIs has been determined using the In- Check Dial device to train twelve non-smoking healthy adult volunteers to inhale at slow (30 Lmin-1) and fast (60 L min-1) inhalation flows through the device with its dial set corresponding to each inhaler. Subsequently each volunteer inhaled at the trained inhalation flows through each active inhaler. The local ethics committee approval was obtained prior to the study and all volunteers gave signed informed consent. The results obtained demonstrate that the studied inhalers have flow-dependent dose emission, thereby enhancing confidence in the use of the In-Check Dial® to identify a patient's inhalation flows through a variety of DPIs. Also the total emitted dose determined by ex-vivo methodology was significantly (p≤0.05) greater with two inhalations than one inhalation per metered dose. The results of the in-vitro aerodynamic dose emission characteristics highlight that the fine particle dose (FPD) from the four studied inhalers is flow dependent. Also the minimum inhalation flow to generate the (FPD) with the appropriate characteristics for lung deposition has been identified to be 20 L min⁻¹ for the Accuhaler®, Easyhaler® and Clickhaler®, while that for the Turbuhaler® is about 30 L min⁻¹. Also the inhalation volume above 2L and the number of inhalations for each dose have respectively no significant (p≤0.05) influence on the FPD emitted from the four studied inhalers. The results support the present instructions to patients using these inhalers to inhale once for each dose as fast as they can.

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43

Potter, Catherine. "Investigating hypnosis for the alleviation of dental anxiety : does the addition of hypnosis to inhalation sedation reduce dental anxiety more than inhalation sedation alone?" Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/investigating-hypnosis-for-the-alleviation-of-dental-anxietydoes-the-addition-of-hypnosis-to-inhalation-sedation-reduce-dental-anxiety-more-than-inhalation-sedation-alone(a48a3842-180e-48a8-951a-aa385cc9fb94).html.

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Chapter 1 reviews the literature. It gives a historical overview of hypnosis. It reviews the literature on dental anxiety, including its prevalence and aetiology. It reviews behavioural and cognitive behavioural treatments of dental fear. Inhalation sedation its mechanism of action, effectiveness and draw-backs are discussed. The literature on hypnosis is selectively reviewed, its use in anxiety and dentistry and lastly, the combination of sedation techniques, particularly IHS, is discussed. It is concluded that evidence for the use of hypnosis for the alleviation of dental anxiety needs to be critically addressed. Chapter 2 presents the published protocol of a Cochrane systematic review followed by qualitative results of this review. 11 studies of generally poor quality were included in the review which concludes that there are significant problems with the evidence due to methodological issues, the different outcome measures used and the generally high or unclear risks of bias. There is some evidence that hypnosis may help patients who have a normal range of dental anxiety but who are undergoing a stressful dental procedure. Studies of phobic patients were characterised by high levels of drop-out behaviour and hypnosis could not be shown to be superior to other forms of behavioural treatment. Chapter 3 describes two studies which aimed to develop a Mood Induction Procedure to induce temporary dental anxiety in volunteers. This was used in two later studies. A non-clinical sample was used as a ‘proof of concept’ study was desirable. Study 1tested excerpts of a film, producing only a medium rise in anxiety (ES r = .49). The second study used a shorter, more concentrated film. This produced a large increase in anxiety (ES r=.86). Heart rate was investigated as a possible physiological measure of anxiety, but was not found useful. Chapter 4 describes two randomised controlled studies aiming to investigate whether hypnosis combined with IHS would reduce the anxiety produced by the film more than a control procedure in which IHS was combined with the reading of a story. These studies suggested there may be some effects attributable to hypnosis, but conclusive benefit was not demonstrated. Chapter 5 presents discussion and the overall conclusions of the thesis. Conclusions include the need for further well designed large scale trials involving hypnosis.

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44

Russell-Lodrigue, Kasi Elizabeth. "An inhalation model of acute Q fever in guinea pigs." [College Station, Tex. : Texas A&M University, 2006. http://hdl.handle.net/1969.1/ETD-TAMU-1209.

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45

Elversson, Jessica. "Spray-Dried Powders for Inhalation : Particle Formation and Formulation Concepts." Doctoral thesis, Uppsala University, Department of Pharmaceutical Chemistry, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5904.

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Spray drying is a method with a high potential in the preparation of protein particles suitable for pulmonary delivery. However, surface induced denaturation of bio-molecules during atomization and subsequent drying can be substantial and it is therefore important to develop new formulation concept for concurrent encapsulation and stabilization of proteins during spray drying. Hence, with an overall objective to increase the knowledge of the formation of particulate systems for systemic administration of proteins by spray drying, the first part of this thesis, systematically investigated the particle formation by droplet size and particle size measurements. It was described how specific properties, such as the solubility and the crystallization propensity of the solute, can affect the product, e.g. the particle size, internal structures, and possibly particle density. A new method using atomic force microscopy (AFM) for the assessment of the effective particle density of individual spray-dried particles was demonstrated. In the second part, two different formulation concepts for encapsulation of protein during spray drying were developed. Both systems used non-ionic polymers for competitive adsorption and displacement of protein from the air/water interface during spray drying. The aqueous two-phase system (ATPS) of polyvinyl alcohol (PVA) and dextran, and the surface-active polymers, hydroxypropyl methylcellulose (HPMC) and triblock co-polymer (poloxamer 188) used for in situ coating, proved efficient in encapsulation of a model protein, bovine serum albumin (BSA). Inclusion of polymeric materials in a carbohydrate matrix also influenced several particle properties, such as the particle shape and the surface morphology, and was caused by changes in the chemical composition of the particle surface and possibly the surface rheology. In addition, powder performance of pharmaceutical relevance, such as dissolution and flowability, were affected.

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46

Claus, Sarah. "Novel dry powder inhalation system based on dispersion of lyophilisates." Diss., Ludwig-Maximilians-Universität München, 2012. http://nbn-resolving.de/urn:nbn:de:bvb:19-159959.

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47

Cordts, Eike [Verfasser]. "Advanced Powder Characterization Techniques for Inhalation Powder Mixtures / Eike Cordts." Kiel : Universitätsbibliothek Kiel, 2014. http://d-nb.info/1064175279/34.

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48

Amann, Elena [Verfasser]. "Pulmonale Inflammationsreaktion bei beatmeten Frühgeborenen unter NO-Inhalation / Elena Amann." Ulm : Universität Ulm. Medizinische Fakultät, 2012. http://d-nb.info/1024533972/34.

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49

Hertel, Mats [Verfasser]. "Einfluss von Lactosefeinanteilen in interaktiven Pulvermischungen zur Inhalation / Mats Hertel." Kiel : Universitätsbibliothek Kiel, 2018. http://d-nb.info/1161409513/34.

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50

Semple, Sean. "Exposure modelling : estimating dermal and inhalation exposures for epidemiological research." Thesis, University of Aberdeen, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.395143.

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This study reviews available methods of exposure assessment, examines the effects of exposure misclassification on the ability to identify an association, and focuses on recent progress in subjective exposure modelling. Subjective exposure modelling utilises a framework of parameters identified as likely to control personal exposure levels together with detailed guidance and expert judgement in order to estimate exposure concentrations. As part of a case-control study, the Neurotoxicity of Paint Solvents (NPS) study, the process of evaluating subjects' lifetime exposure to solvents was reviewed. A training program and detailed guidance material was produced and the ability of assessors to reconstruct inhalation exposures from textual data was tested. In the training study, assessors were shown to estimate exposures that were well correlated with measured levels (correlation coefficients for log estimate compared to log measured values ranging from 0.73 to 0.85). The assessors tended to overestimate levels with the estimates ranging from 1.6 to 3.5 times the measured results. A series of painting simulation exercises was carried out to validate the use of certain guidance values for the model parameters. Using different paint application methods and different paint types, the influence of these variables on exposure levels was assessed. The results agreed closely with the guidance produced for the inhalation exposure model. Analysis of the solvent exposure histories of the NPS study group suggested that dermal exposure and uptake of solvents was important. To this end a novel dermal exposure model was developed for spray painting tasks. Using a conceptual model of the process, a method to describe both the likely dermal solvent exposure and solvent uptake through the skin was created. Mechanisms for combining exposures from the dermal and inhalation exposure pathways are described. Using occupational history information together with workplace monitoring records and data from paint manufacturers, both inhalation and dermal exposure to solvents was estimated for the one-hundred and twenty NPS study subjects. Two solvent exposure metrics were calculated. Cumulative exposure was the product of exposure level and time, while average annual intensity was the cumulative exposure figure divided by the number of years in solvent using employment.

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Dissertations / Theses on the topic 'Inhalation'

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