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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
31

Characterization Of Skeletal Muscle Lipids In Obese Mice Lines

Aras, Ebru 01 September 2012 (has links) (PDF)
Obesity becomes an epidemic health problem in developing and developed countries, which arises due to stable life style and increase in the consumption of high fat diets. Obesity is generally accompanied with various clinical disorders, such as insulin resistance, type II diabetes, hypertension, dyslipidemia and cardiovascular diseases. This study aims to characterize and quantify different lipid classes in longissimus dorsi (LD) and quadriceps (Q) skeletal muscles of control (DBA/2J), obese Berlin fat mouse inbred (BFMI) and Berlin muscle mouse inbred (BMMI) lines, which display high fat and high muscle content, respectively. These mouse lines were special due to their phenotypes, especially BFMI lines, which displayed spontaneous and strong obesity. These lines, more specifically BFMI860 and BFMI861, were also special due to their possibility of being an animal model of cardiovascular diseases and metabolic syndrome, since they also displayed insulin resistance. For separation,identification and quantification of various lipids of these lines, a novel method was developed which gives better separation of main lipid classes via using high performance liquid chromatography (HPLC) coupled to an evaporative light scattering detector (ELSD). Addition of triethylamine (TEA) to the solvents being used, and altering the parameters of HPLC and ELSD instruments, and also the gradient elution, provided a better separation with an enhanced resolution. This method has been applied to the lipid extracts obtained from longissimus dorsi (LD) and quadriceps (Q) skeletal muscles of control (DBA/2J), obese Berlin fat mouse inbred (BFMI) and Berlin muscle mouse inbred (BMMI). In this method, a binary gradient elution composed of n-Hexane, isopropanol, methanol, acetic acid and triethylamine was applied to the samples. All interested lipid classes, namely triglyceride (TG), cholesteryl ester (CO), cholesterol (C), 1-oleoyl-rac-glycerol (MG), phosphatidylcholine (PC) and cardiolipin (CLPN), all of which have been known to have a role in obesity, insulin resistance, and cardiovascular diseases, were separated, identified and quantified via this novel method. According to the results, among BFMI lines, BFMI860 and BFMI861 lines and BMMI806, among BMMI lines, are worth to study obesity. Especially, the former ones may also become animal models for cardiovascular diseases and metabolic syndrome.
32

Pantametoden : En metod som alternativ för att skapa ljuddesign

Sonesson, Daniel, Öhman, Olle January 2015 (has links)
I detta arbete har vi försökt skapa en metod som skulle kunna hjälpa ljuddesigners inomindieföretag att med begränsade resurser komma fram till en kvalitativ ljuddesign genom attanvända en form av återvinning. Syftet med vår metod, som vi kallar för pantametoden, går utpå att återvinna ljudmaterial med hjälp av effekter för att skapa nya och kreativa ljud som går attanvända i en produktion. Vi kommer att gå igenom de nödvändigaste delarna för att visa hur vitillämpat vår metod, exempelvis vilka verktyg som finns och hur de kan användas för att uppnådet resultat som eftersträvas. Metoden har testats på två stycken spel som vi har varit med ochutvecklat, och där vi har bidragit med ljuddesignen med hjälp av vår metod. Vi kommer attpresentera vilket resultat vi har uppnått, och vilka problem som har uppstått. / In this thesis we have tried to create a method that could help sound designers within the indiecommunity, often having limited resources, to achieve a sound design that holds a good qualityby using a kind of recycling. The purpose of our method, which we call “pantametoden”, isabout reusingsound material with the help of different effects that can help creating new andcreative sounds possible to use in a production. We will demonstrate the necessary parts toillustrate how we have used our method, for example which tools there are and how they can beused in order to achieve desirable results. The method has been tested on two games which wehave participated in developing and where we have contributed with the sound design by usingour method. We will present the results achieved and what kind of problems we have encountered.
33

Organophosphates and phthalates in air and dust from indoor environments : Method development and applied measurements

Bergh, Caroline January 2011 (has links)
Organophosphate and phthalate esters are polymer additives that are frequently found in air and dust in indoor environments. This thesis describes the development and application of air sampling and selective mass spectrometric (MS) determination of these two compound groups. It also describes the sampling and screening of these compounds in indoor air and dust from different environments and the development and evaluation of a method for the extraction and determination of these compounds in indoor dust. An air sampling method previously used for air sampling of only organophosphate esters, is here demonstrated to be applicable for simultaneous sampling of both phthalate and organophosphate esters. Selective detection using tandem mass spectrometry (MS/MS) showed good results for simultaneous determination of organophosphate and phthalate esters in air. The high selectivity of this technique was especially advantageous when analyzing dust. Comparison of chemical profiles of the organophosphate ester between indoor environments including daycare centers, offices and private homes differed between the types of locations while the phthalate profiles were rather similar. Comparison of concentration levels of these compounds in multi-storey apartment buildings classified as either high or low risk “sick” buildings could not differentiate the two classes of buildings. Further, the studies also points out some potential sources of organophosphate and phthalate esters in these indoor environments. In general the levels of phthalate esters were consistently higher than the levels of organophosphate esters both in air and in dust. Phthalate and organophosphate esters were also determined in a dust standard reference material; seventeen of the targeted compounds were quantified out of which ten had not previously been reported for this reference material. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Submitted. Paper 4: Manuscript.</p>
34

Mätning av viskositet på stärkelse / Measurement of the viscosity of starch

Löfgren, Mikael January 2015 (has links)
Stärkelse används vid papperstillverkning för att öka styrkeegenskaperna hos pappret. Denna stärkelse kan av olika anledningar brytas ned och bli sämre, då främst på grund av bakterier. Detta kan leda till försämrad papperskvalitet och i värsta fall kassationer av slutprodukten. För att undersöka om stärkelsen blivit angripen av bakterier kan man göra en bakterieodling. Nackdelen med detta är att det tar väldigt lång tid innan man ser något resultat. En annan effekt av bakterierna är att stärkelsens viskositet blir lägre, dvs. vätskan blir mindre trögflytande. Detta är en parameter som kan mätas med en viskometer. Syftet är att utarbeta en ny mätstandard för att detektera bakteriella angrepp, där den främsta fördelen är att mätmetoden ger en snabb och säker respons och därmed minskar reaktionstiden för att motverka bakterierna. Målet med examensarbetet är att mäta viskositeten på stärkelse kokad i bruket samt på stärkelse kokad på labb och därmed börja bygga upp en databas med värden för att validera viskometern. Arbetet har utförts i laboratoriet på Tech Center vid Smurfit Kappa, Piteå. En viktig upptäckt som gjordes var att pH-värdet kan vara lågt men det betyder nödvändigtvis inte att man har ett bakterieangrepp. Arbetet begränsas väldigt mycket av tidsperioden på fem veckor och det är möjligt att fler mätningar skulle ge ett annat resultat. De mätningar som gjorts tyder dock på att det går att mäta viskositeten på stärkelsen dag till dag och att parametern kommer att vara oförändrad så länge koncentrationen är konstant. Arbetet med insamling av mätdata från labbkokad stärkelse samt stärkelse kokad i jetkokare på bruket är en början till att validera metoden. Fler mätningar kommer att utföras för att kunna föra statistik på viskositeten. Punkter som temperatur och koncentrationsgradienters effekt på viskositeten kommer att utvärderas. Målet är att kunna korrigera för dessa så att man i slutändan ska kunna korrelera data till bakteriella angrepp. Om detta lyckas är nästa steg att implementera metoden som en standard på laboratoriet. / Starch is used in papermaking to increase the strength properties of the paper. The starch can for various reasons degrade and become worse, primarily due to bacteria. This can lead to poor paper quality and in worst case to rejects of the final product. To investigate whether the starch has become infested with bacteria, a bacteria culture can be made. The downside of this is that it takes very long time before any results can be seen. Another effect of the bacteria is that the viscosity of the starch gets lower, i.e. the liquid becomes less viscous. This is a parameter that can be measured with a viscometer. The aim is to develop a new measurement standard for detecting bacterial attacks, where the main advantage is that the method provides a quick and reliable response, thus reducing the reaction time to counteract the bacteria. The goal of the project is to measure the viscosity of starch cooked in the mill and starch cooked in the lab and by doing so, start to build up a database of values to validate the viscometer. The work has been carried out in the laboratory at Tech Center at Smurfit Kappa, Piteå. An important discovery was made that the pH may be low but it does not necessarily have to be a bacterial attack. The work is limited a lot by the time period of five weeks and it is possible that more measurements would produce a different result. The measurements made suggest that it is possible to measure the viscosity of the starch from one day to another and that the parameter will remain unchanged as long as the concentration is constant. The work of collecting data from lab cooked starch and starch cooked in the jet boiler at the mill is the beginning to validate the method. More measurements will be carried out in order to keep statistics of the viscosity. Factors like temperature and concentration’s effects on the viscosity will be evaluated. The goal is to correct for these in order to be able to correlate data to a bacterial infestation. If successful, the next step is to implement the method as a standard in the laboratory.
35

Membrane-mimetic systems : Novel methods and results from studies of respiratory enzymes

Nordlund, Gustav January 2013 (has links)
The processes localized to biological membranes are of great interest, both from a scientific and pharmaceutical point of view. Understanding aspects such as the detailed mechanism and regulation of these processes requires investigation of the structure and function of the membrane-bound proteins in which they take place. The study of these processes is often complicated by the need to create in vitro systems that mimic the environment in which these proteins are normally found in vivo. This thesis describes some of the methods available for membrane-protein studies in membrane-mimetic systems, as well as our work aimed at developing such systems. Furthermore, results from studies using these systems are described. In the first two studies, described in Papers I &amp; II, we investigated the use of silica particle-supported lipid bilayers, both for membrane-protein studies and as possible drug-delivery vehicles. Successful reconstitution of a multisubunit proton-pump, cytochrome c oxidase is described and characterized. Initial attempts to develop drug-delivery systems with two different targeting peptides are also described in the thesis. The second part of this thesis revolves around our work with membraneprotein dependent pathways. Results from studies of systems where the proton- pump bo3 oxidase and ATP synthase work in concert are described. The results show a surprising lipid-composition dependence for the coupled bo3- ATP-synthase activity (Paper III). Finally, a new system utilizing synaptic vesicle-fusion proteins for coreconstitution of membrane proteins is described, showing successful coreconstitution of a small respiratory chain, delivery of soluble proteins to preformed liposomes and reconstitution of ATP synthase in native membranes (Paper IV). / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.</p>
36

A Test Method for the Evaluation of Soil Microbial Health in a Petroleum Hydrocarbon Contaminated Boreal Forest Soil

Rahn, Jessica Hillary 15 May 2012 (has links)
A standardized method to examine soil microbial health incorporating biomass, activity, and diversity measurements is currently lacking, limiting the use of this ecologically relevant endpoint in ecological risk assessments. The soil microbial health of a petroleum hydrocarbon-contaminated boreal forest soil, relative to a reference soil, was examined using a suite of tests. Microbial health impacts in the contaminated soil were observed using nitrification, organic matter decomposition, bait lamina, denaturing gradient gel electrophoresis, community level physiological profiling, and most enzyme assays. Results of heterotrophic plate count and respiration tests indicated higher culturable numbers and activity in the contaminated soil. A data integration technique was developed to incorporate the results from individual tests into an overall conclusion, indicating that soil contamination at the site moderately to severely impacted microbial health. The research presented lays the foundation for the development of a soil microbial health standardized method.
37

Development of a stability indicating HPLC method for the Pheroid™ delivery system / Elaine van den Berg

Van den Berg, Elaine January 2010 (has links)
Stability plays an important role in the development of a new drug product. High Performance Liquid Chromatography (HPLC) is considered a stability indicating method of analysis. It is widely used in the pharmaceutical industry for the quantification of small organic molecules during stability testing. Previous stability studies conducted on Pheroid™-based drug products, experienced problems with the generation of reliable data by means of HPLC analysis. With these studies it was concluded that the inconclusive results could either be attributed to the stability of the delivery system itself and the compatibility of the active pharmaceutical ingredients (API's) with the delivery system, or to the usage of unsuitable HPLC methods. The aims of this study were to: i. determine if the Pheroid™ delivery system changes significantly over time at accelerated storage conditions and how these changes influence the HPLC analysis, ii. determine the effect of the anti-oxidant tert-butylhydroquinone (TBHQ) on the stability and HPLC analysis of the Pheroid™ delivery system, and iii. to suggest a suitable approach for the analysis of Pheroid™-based drug products. Pheroid™ microsponges, containing no API's, were prepared and stored for a period of three months at 5°C, 25°C+60%RH, 30°C+65%RH and 40°C+75%RH. Two of the four Pheroid™ formulations contained an extra anti-oxidant, namely TBHQ. Monthly HPLC analyses were done using existing methods for mefloquine and artesunate. In addition to HPLC analysis, particle size analysis and Confocal Laser Scanning Microscopy (CLSM) were undertaken to support the HPLC results and provide information concerning the overall stability of the Pheroid™ delivery system. After the completion of the above analyses, experiments were carried out to determine whether adjustments to some of the key chromatographic parameters could improve the separation of Pheroid™-based samples. The parameters that were subjected to change included the organic solvent, isocratic versus gradient separation, pH and detection wavelength. Two pro-Pheroid vesicles formulations were prepared and stored for a three month period at 40°C+75%RH only. No API was added to the one formulation while the other contained 2 mg/ml of mefloquine hydrochloride. Results obtained indicated that the Pheroid™ formulations changed after exposure to elevated temperature and humidity. The number of detectable peaks increased, longer run times became necessary and solubility in the sample solvent (methanol) decreased. Solubility of the Pheroid™ formulations in methanol was preserved to some extent by the presence of TBHQ. Physical signs of instability like discolouration and creaming were noted for TBHQ-containing formulations. TBHQ also seemed to have influenced the particle sizes, particle size distributions and structure of the Pheroid™ microsponges. With adjustments made to the HPLC method it was found that: i. the sample solvent is incompatible with the HPLC system, ii. very hydrophobic compounds are present in the Pheroid™-based samples, iii. acetontrile and methanol are unsuitable for both gradient and isocratic separation of Pheroid™-based samples, iv. more Pheroid™ components absorb at shorter wavelengths, and v. small changes in the pH values usually implemented do not influence the retention and selectivity of the Pheroid™ components. The Pheroid™ delivery system proved to be too complex and reversed hydrophobic for phase HPLC analysis. Preparation of the sample by only diluting the Pheroid™ formulations with pure methanol was not optimal. These samples introduced compounds to the column of which some caused interferences with the analyte peak while others were difficult to elute from the column. To continue using HPLC for the analysis of Pheroid™-based drug products, it is therefore recommended that attention should be given to the development of a more appropriate sample preparation procedure, like solid phase extraction or liquid-liquid extraction, one that will eliminate the effects of the Pheroid™ components. Physical instabilities noticed with the addition of TBHQ, suggest that there should also be attended to the compatibility and stability of each of the components in the Pheroid™ delivery system during formulation development. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.
38

Development of a stability indicating HPLC method for the Pheroid™ delivery system / Elaine van den Berg

Van den Berg, Elaine January 2010 (has links)
Stability plays an important role in the development of a new drug product. High Performance Liquid Chromatography (HPLC) is considered a stability indicating method of analysis. It is widely used in the pharmaceutical industry for the quantification of small organic molecules during stability testing. Previous stability studies conducted on Pheroid™-based drug products, experienced problems with the generation of reliable data by means of HPLC analysis. With these studies it was concluded that the inconclusive results could either be attributed to the stability of the delivery system itself and the compatibility of the active pharmaceutical ingredients (API's) with the delivery system, or to the usage of unsuitable HPLC methods. The aims of this study were to: i. determine if the Pheroid™ delivery system changes significantly over time at accelerated storage conditions and how these changes influence the HPLC analysis, ii. determine the effect of the anti-oxidant tert-butylhydroquinone (TBHQ) on the stability and HPLC analysis of the Pheroid™ delivery system, and iii. to suggest a suitable approach for the analysis of Pheroid™-based drug products. Pheroid™ microsponges, containing no API's, were prepared and stored for a period of three months at 5°C, 25°C+60%RH, 30°C+65%RH and 40°C+75%RH. Two of the four Pheroid™ formulations contained an extra anti-oxidant, namely TBHQ. Monthly HPLC analyses were done using existing methods for mefloquine and artesunate. In addition to HPLC analysis, particle size analysis and Confocal Laser Scanning Microscopy (CLSM) were undertaken to support the HPLC results and provide information concerning the overall stability of the Pheroid™ delivery system. After the completion of the above analyses, experiments were carried out to determine whether adjustments to some of the key chromatographic parameters could improve the separation of Pheroid™-based samples. The parameters that were subjected to change included the organic solvent, isocratic versus gradient separation, pH and detection wavelength. Two pro-Pheroid vesicles formulations were prepared and stored for a three month period at 40°C+75%RH only. No API was added to the one formulation while the other contained 2 mg/ml of mefloquine hydrochloride. Results obtained indicated that the Pheroid™ formulations changed after exposure to elevated temperature and humidity. The number of detectable peaks increased, longer run times became necessary and solubility in the sample solvent (methanol) decreased. Solubility of the Pheroid™ formulations in methanol was preserved to some extent by the presence of TBHQ. Physical signs of instability like discolouration and creaming were noted for TBHQ-containing formulations. TBHQ also seemed to have influenced the particle sizes, particle size distributions and structure of the Pheroid™ microsponges. With adjustments made to the HPLC method it was found that: i. the sample solvent is incompatible with the HPLC system, ii. very hydrophobic compounds are present in the Pheroid™-based samples, iii. acetontrile and methanol are unsuitable for both gradient and isocratic separation of Pheroid™-based samples, iv. more Pheroid™ components absorb at shorter wavelengths, and v. small changes in the pH values usually implemented do not influence the retention and selectivity of the Pheroid™ components. The Pheroid™ delivery system proved to be too complex and reversed hydrophobic for phase HPLC analysis. Preparation of the sample by only diluting the Pheroid™ formulations with pure methanol was not optimal. These samples introduced compounds to the column of which some caused interferences with the analyte peak while others were difficult to elute from the column. To continue using HPLC for the analysis of Pheroid™-based drug products, it is therefore recommended that attention should be given to the development of a more appropriate sample preparation procedure, like solid phase extraction or liquid-liquid extraction, one that will eliminate the effects of the Pheroid™ components. Physical instabilities noticed with the addition of TBHQ, suggest that there should also be attended to the compatibility and stability of each of the components in the Pheroid™ delivery system during formulation development. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.
39

EYE TRACKING IN USABILITY : A methodology study

Hedlund, John January 2018 (has links)
The usability group at RISE Research Institute of Sweden primarily perform usability evaluations for their clients. Usability evaluations are performed on launched products as well as early prototypes, the purpose of these evaluations is to detect problems and give suggestions on how they can be solved. The usability group offers a variety of usability evaluations, such as expert evaluations where experts assess the usability of a product and user tests were participants are observed when preforming tasks with a product. Eye tracking is a relatively new tool that measures eye movement; this tool is used within the usability group at RISE today, mostly as a compliment in usability tests. No extensive analysis is made of the data collected using eye tracking, due to lack of time, resources and knowledge. The purpose of this project is to investigate whether and, if so, how eye tracking can be used efficiently to evaluate usability in user tests. At the start of the project a literature study, an analysis of the current state was carried out along with a practical exploration of the eye tracking technology and associated analysis tools. Based on the information gathered in the first part of the project, two directions were selected. A qualitative approach, with the aim of exploring and explaining why a usability issue arises, and a quantitative approach with the aim to compare two equivalent products and determining which one of them is best in a usability perspective. Early in the project challenges with the collection and evaluating eye tracking data were identified. These challenges were largely related to how a usability test is conducted. In order to further explore how to best perform a usability test using eye tracking, a pilot study was conducted in which the test object was a microwave oven. The goal of the pilot study was to develop a test setup to be able to collect eye tracking data with minimal impact on factors affecting the eye tracking data. Examples of factors are "think aloud" and that the test moderator asks questions during when the participant perform a task. Based on the insights from the pilot study, the test setup was further developed, and both a qualitative and quantitative method of data collection and analysis was developed. The test setup and the two methods were evaluated in a usability test with two clock radios. The results of the tests in this project show that the qualitative analysis of eye tracking data can gather detailed data on how a person searches for information when performing a given task. By looking at the eye movement pattern, you can get indications of shortcomings in the information layout of a particular product. Eye tracking allows you to understand why a person fails a task by checking if the test person saw the desired information without interpreting it or if the person completely missed the information that was necessary to complete the task. The quantitative analysis of eye tracking data could not detect any differences between the products tested to indicate differences in the overall usability. The conclusion is that a qualitative analysis is the most effective way to utilize eye tracking in usability tests of consumer products. / Usability-gruppen på RISE Research Institute of Sweden arbetar främst med att utvärdera användbarhet på produkter för olika kunder. Användbarhets-utvärderingar utförs på lanserade produkter så väl som tidiga prototyper. Syftet med dessa utvärderingar är att upptäcka problem relaterade till användbarhet och komma med förslag på hur problemen kan lösas. Usability-gruppen erbjuder en rad olika typer av utvärderingar av produkter, exempelvis expertutvärderingar där produktens användbarhet bedöms av experter, och användartester där man observerar när en testperson använder en produkt. Eye tracking är ett relativt nytt verktyg som mäter ögonrörelser, detta verktyg används inom usability- gruppen på RISE idag som ett komplement vid använbarhets-tester. Då man saknar tid, resurser och till viss del kunskap om verktygets tillämpning används eye tracking idag endast som ett passivt verktyg. Med detta menas att man samlar in data utan att utföra några djupare analyser. Syftet med detta examensarbete är att undersöka om och i så fall hur eye tracking kan användas på ett effektivt sätt för att utvärdera användbarhet i användartester. I starten av projektet genomfördes en litteraturstudie, en nulägesanalys samt praktisk utforskning av tekniken och tillhörande analysverktyg. Baserat på den information som samlades in i första delen av projektet valdes två inriktningar. En kvalitativ inriktning, med målet att utforska och förklara varför ett visst användbarhetsproblem uppstår, och en kvantitativ inriktning med målet att jämföra två likvärdiga produkter och bestämma vilken av dessa som har bäst användbarhet. Tidigt identifierades även utmaningar med insamling och utvärdering av eye tracking-data, dessa utmaningar visade sig till stor del bero på hur ett användartest genomförs. För att vidare utforska hur man bäst genomför ett användbarhets-test med hjälp av eye tracking gjordes därför en så kallad pilotstudie där testobjektet var en mikrovågsugn. Målet med denna var att hitta ett testupplägg för att samla in eye tracking-data med minimal påverkan av omgivande faktorer som påverkar datan. Exempel på faktorer skulle kunna vara att testpersonen får ”tänka högt” eller att testledaren ställer frågor under genomförandet av en uppgift. Baserat på insikterna från pilotstudien vidareutvecklades testupplägget, och både en kvalitativ såväl som kvantitativ metod för datainsamling och analys togs fram. Testupplägget och de två metoderna utvädrades genom ett användbarhetstest där två olika klockradios testades. Resultaten från testerna som genomförts i projektet visar att man med kvalitativ analys av eye tracking data kan samla in detaljerade data på hur en person letar efter information vid utförande av en given uppgift. Genom att titta på ögonens rörelsemönster kan man få indikationer på brister i informationslayouten på en viss produkt. Med hjälp av eye tracking kan man förstå varför en person misslyckas med en uppgift genom att se om testpersonen såg den önskade informationen utan att tolka den eller om personen helt missade den information som var nödvändig för att klara uppgiften. Den kvantitativa analysen av eye tracking data kunde inte påvisa några skillnader mellan de produkter som testades för att indikera skillnader i användbarhet. Slutsatsen är att en kvalitativ analys är det effektivaste sättet att nyttja eye tracking vid användbarhetstester av konsumentprodukter.
40

The physical chemistry of pMDI formulations derived from hydrofluoroalkane propellants : a study of the physical behaviour of poorly soluble active pharmaceutical ingredients : bespoke analytical method development leading to novel formulation approaches for product development

Telford, Richard January 2013 (has links)
Active Pharmaceutical Ingredients (APIs) are frequently prepared for delivery to the lung for local topical treatment of diseases such as Chronic Obstructive Pulmonary Disease (COPD) and asthma, or for systemic delivery. One of the most commonly used devices for this purpose is the pressurised metered dose inhaler (pMDI) whereby drugs are formulated in a volatile propellant held under pressure. The compound is aerosolised to a respirably sized dose on actuation, subsequently breathed in by the user. The use of hydrofluoroalkanes (HFAs) in pMDIs since the Montreal Protocol initiated a move away from chlorofluorocarbon (CFC) based devices has resulted in better performing products, with increased lung deposition and a concomitant reduction in oropharyngeal deposition. The physical properties of HFA propellants are however poorly understood and their capacity for solubilising inhaled pharmaceutical products (IPPs) and excipients used historically in CFCs differ significantly. There is therefore a drive to establish methodologies to study these systems in-situ and post actuation to adequately direct formulation strategies for the production of stable and efficacious suspension and solution based products. Characterisation methods have been applied to pMDI dosage systems to gain insight into solubility in HFAs and to determine forms of solid deposits after actuation. A novel quantitative nuclear magnetic resonance method to investigate the physical chemistry of IPPs in these preparations has formed the centrepiece to these studies, accessing solubility data in-situ and at pressure for the first time in HFA propellants. Variable temperature NMR has provided thermodynamic data through van’t Hoff approaches. The methods have been developed and validated using budesonide to provide limits of determination as low as 1 μg/mL and extended to 11 IPPs chosen to represent currently prescribed inhaled corticosteroids (ICS), β2-adrenoagonists and antimuscarinic bronchodilators, and have highlighted solubility variations between the classes of compounds with lipophilic ICSs showing the highest, and hydrophilic β2- agonist/antimuscarinics showing the lowest solubilities from the compounds under study. To determine solid forms on deposition, a series of methods are also described using modified impaction methods in combination with analytical approaches including spectroscopy (μ-Raman), X-ray diffraction, SEM, chromatography and thermal analysis. Their application has ascertained (i) physical form/morphology data on commercial pMDI formulations of the ICS beclomethasone dipropionate (QVAR®/Sanasthmax®, Chiesi) and (ii) distribution assessment in-vitro of ICS/β2-agonist compounds from combination pMDIs confirming co-deposition (Seretide®/Symbicort®, GlaxoSmithKline/AstraZeneca). In combination, these methods provide a platform for development of new formulations based on HFA propellants. The methods have been applied to a number of ‘real’ systems incorporating derivatised cyclodextrins and the co-solvent ethanol, and provide a basis for a comprehensive study of solubilisation of the ICS budesonide in HFA134a using two approaches: mixed solvents and complexation. These new systems provide a novel approach to deliver to the lung, with reduced aerodynamic particle size distribution (APSD) potentially accessing areas suitable for delivery to peripheral areas of the lung (ICS) or to promote systemic delivery.

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