Browsing by Subject "dry powder inhaler"

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  • Autio, Maiju (Helsingfors universitet, 2011)
    Generation of raw materials for dry powder inhalers by different size reduction methods can be expected to influence physical and chemical properties of the powders. This can cause differences in particle size, size distribution, shape, crystalline properties, surface texture and energy. These physical properties of powders influence the behaviour of particles before and after inhalation. Materials with an amorphous surface have different surface energy compared to materials with crystalline surface. This can affect the adhesion and cohesion of particles. Changes in the surface nature of the drug particles results in a change in product performance. By stabilization of the raw materials the amorphous surfaces are converted into crystalline surfaces. The primary aim of the study was to investigate the influence of the surface properties of the inhalation particles on the quality of the product. The quality of the inhalation product is evaluated by measuring the fine particle dose (FPD). FDP is the total dose of particles with aerodynamic diameters smaller than 5,0 µm. The secondary aim of this study was to achieve the target level of the FPD and the stability of the FPD. This study was also used to evaluate the importance of the stabilization of the inhalation powders. The study included manufacturing and analysing drug substance 200 µg/dose inhalation powder batches using non-stabilized or stabilized raw materials. The inhaler formulation consisted of micronized drug substance, lactose <100µm and micronized lactose <10µm. The inhaler device was Easyhaler®. Stabilization of the raw materials was done in different relative humidity, temperature and time. Surface properties of the raw materials were studied by dynamic vapour sorption, scanning electron microscopy and three-point nitrogen adsorption technique. Particle size was studied by laser diffraction particle size analyzer. Aerodynamic particle size distribution from inhalers was measured by new generation impactor. Stabilization of all three raw materials was successful. A clear difference between nonstabilized and stabilized raw materials was achieved for drug substance and lactose <10µm. However for lactose <100µm the difference wasn't as clear as wanted. The surface of the non-stabilized drug substance was more irregular and the particles had more roughness on the surface compared to the stabilized drug substances particles surface. The surface of the stabilized drug particles was more regular and smoother than non-stabilized. Even though a good difference between stabilized and non-stabilized raw materials was achieved, a clear evidence of the effect of the surface properties of the inhalation particles on the quality of the product was not observed. Stabilization of the raw materials didn't lead to a higher FPD. Possible explanations for the unexpected result might be too rough conditions in the stabilization of the drug substance or smaller than wanted difference in the degree of stabilization of the main component of the product <100µm. Despite positive effects on the quality of the product were not seen there appears to be some evidence that stabilized drug substance results in smaller particle size of dry powder inhalers.
  • von Schantz, Sofia (Helsingfors universitet, 2015)
    This study aims to address how easily an individual with no prior inhaler experience can learn to use a dry powder inhaler (DPI) through video education. This is a comparative study of four DPIs (Diskus, Easyhaler, Ellipta and Turbuhaler). Different properties affecting ease of use, patient preference as well as educational videos as a method of providing inhaler instructions were investigated. The study used a triangular methodology. The sample consisted of 31 individuals (24-35 years). All participants were considered inhaler naïve. After watching the video education material for a particular inhaler the participants' demonstrated the use of it. Educational videos for all four inhalers were watched and use of all placebo inhalers was demonstrated in a random order. These demonstrations were videotaped. The demonstrations were thereafter checked against a predefined checklist and all mistakes were recorded. Only 33 % of inhaler demonstrations were completed without the participants making any mistakes that could compromise the efficacy of the inhaled medication in a real-life situation. The frequency of error varied greatly between different types of inhalers. Ellipta proved to be most often used correctly with 55 % demonstrating use without making any mistakes. This was closely followed by Diskus for which 48 % demonstrated correct use. The difference between the average error frequency for Ellipta and Diskus was statistically insignificant. With Easyhaler 19 % percent of participants were able to demonstrate correct use, the corresponding percentage for Turbuhaler was 16 %. When comparing participants' demonstrations for Easyhaler and Turbuhaler, the difference in average error frequency between the devices were not statistically significant. The average frequency of error was lower when using Ellipta in comparison to Easyhaler and Turbuhaler (statistically significant). The same indications were found when comparing average frequency of error for Diskus, to those for Easyhaler and Turbuhaler. Comparing the participants self-reported correct use against the actual numbers it is clear that participants often thought they were using the inhaler correctly when they in fact were not. When asked to rank the inhalers from most preferred to least preferred, Ellipta emerged as a favorite. Turbuhaler received the second highest scores, Diskus the third and Easyhaler was least preferred. However, only the difference between preference scores for Ellipta and Easyhaler was deemed statistically significant. The high frequency of error suggests that even though participants generally considered the inhalers intuitive and easy to use, they would have required more comprehensive inhaler education in order to achieve correct inhaler technique. Further, the results indicate that video demonstrations are not ideal for providing inhaler education for first time inhalers users. The most prominent problem with video education is that it provides no feedback to the user regarding their inhaler technique. This may present real problems as the results of this study show that participants tended to overestimate their own inhaler technique. Patient education plays a central role in asthma care and needs to be given proper attention even though the inhalers might be considered intuitive and easy to operate. Interesting areas for future research include investigating interactive learning videos as a way of improving video education on inhaler technique.
  • Savelainen, Timo (Helsingfors universitet, 2013)
    Some problems in dry powder inhaler formulation include low dose efficiency and changes in dispersibility during storage. For lung deposition particles should have aerodynamic size of 1 - 5µm. Poor dispersion of drug particles from carriers' surface is thought to be the main reason for low dose efficacy. A tertiary component of small particles has been generally added to formulation to improve fine particle dose. Small particles are usually manufactured by micronization. This may induce crystal defects and amorphous sites on the surface of crystals. Amorphous sites are metastable and they may crystallize during storing. Changes in particles crystallinity may have an action on efficiency and stability of dry powder inhalers. Conditioning is designated as stabilisation of particles surface by mixture of solvent vapour and inert gas. Vapour may also dissolve surface roughness. This is called deliquescence. Ostwald ripening is phenomenon whereby small particles dissolves and recrystallizes onto larger crystals. This can be extended for surface asperities. Amorphous materials have also better solubility than crystalline materials so amorphous sites may also dissolve and recrystallize onto crystalline surface. Amorphous sites may crystallize spontaneously by absorbing plasticizing agents from vapour phase or by influence of temperature. The purpose of this work was to study process variables in conditioning and their effect on modification of surface roughness and stabilization of micronized α-lactose monohydrate and test drug substance. The purpose was also to study how surface modification and stabilization effects on powders flowability and stability of dry powder inhaler. The dry powder inhaler contained two different vicinity of lactose and two different drug substances. Conditioning was based on evaporation of liquid from open surface. Studied process variables were temperature of powder, temperature of bath of liquid phase and flow rate of nitrogen gas. The aim of this study was to form a process design for conditioning of new substances, to improve powders flowability and to remove changes in fine particle dose during storage. Surface roughness was studied by laser diffraction analysis and specific surface area measurements and also by electron microscopy. Specific surface area was measured by nitrogen adsorption method. Stabilization of amorphous sites ware studied by dynamic vapour sorption. Flowability was measured by angle of repose and with FlowPro device. Fine particle dose was measured with next generator impactor device. The study showed that increasing the amount of solvent in vapour increases surface smoothness and stabilization. Also increase of temperature of sample increased stabilization. Influence of temperature on surface smoothness was not as clear. Changes in temperature may have altered adsorption and kinetic of crystallization of dissolved molecules. Flowability of lactose was significantly improved. Condition did not improve dry powder inhalers fine particle dose, but there was significant difference between different process conditions. This was concluded to be caused of surface modification. It was also shown that different process conditions affected on formulations stability.