No description available.

Combination inhaled corticosteroids (ICs) are the primary treatment prescribed for patients with asthma; however, voice problems are also associated with ICs. In this study, 32 rabbits were assigned randomly to one of five experimental groups: baseline, induction, induction control, reversibility, and reversibility control. The baseline group received no treatment and larynges were obtained following quarantine. Rabbits belonging to experimental groups received IC treatment twice a day until trained raters noted visible vocal fold changes during endoscopy, which was performed every 2 weeks. When changes were observed, animals were euthanized, and the larynges were harvested from the experimental induction group and the corresponding control group. The remaining rabbits entered a withdrawal phase wherein ICs were discontinued, and endoscopy was performed every 2 weeks until visual-perceptual ratings indicated a return to baseline. Subsequently, all excised larynges underwent benchtop phonation trials to acquire aerodynamic data relating to vocal fold functioning at phonation onset. Analysis included 17 rabbits from the previous phase of the study and showed an increase in phonation threshold pressure (PTP) and phonation threshold flow (PTF) following IC use compared to the control groups. Rabbits in the experimental withdrawal group showed lower PTP and PTF compared to the induction group, but still greater values than the control groups. These results indicate IC-related adverse vocal effects may decrease after treatment is withdrawn but might not reverse completely. These findings indicate a trend toward recovery when ICs are withdrawn but lay critical groundwork for future studies involving asthma management and IC-driven voice disorders.

No description available.

An issue of inhalation therapy is a complex topic, actively discussed in last decades, and its progress in various scientific fields is more than required. First part of this thesis brings a theoretical introduction into principles of aerosol therapy and into the requirements resulting from them. Commonly available technologies of inhalers and nebulisers for medical usage, parameters that determinate their effectivity are briefly described. Usage mistakes influencing the effectivity of inhalation are discussed, as well. Second part deals with experimental measurements of aerosol that selected inhalers generate. It also describes difficulties connected with the methods of these measurements, with sampling and following analyses. Gained results are compared with an available literature.

This research was aimed at the development and validation of new in vitro methods capable of predicting in vivo drug deposition from dry powder inhalers, DPIs, in lung-normal human adults. Three physical models of the mouth, throat and upper airways, MT-TB, were designed and validated using the anatomical literature. Small, medium and large versions were constructed to cover approximately 95% of the variation seen in normal adult humans of both genders. The models were housed in an artificial thorax and used for in vitro testing of drug deposition from Budelin Novolizer DPIs using a breath simulator to mimic inhalation profiles reported in clinical trials of deposition from the same inhaler. Testing in the model triplet produced results for in vitro total lung deposition (TLD) consistent with the complete range of drug deposition results reported in vivo. The effect of variables such as in vitro flow rate were also predictive of in vivo deposition. To further assess the method’s robustness, in vitro drug deposition from 5 marketed DPIs was assessed in the “medium” MT-TB model. With the exception of Relenza Diskhaler, mean values for %TLD+SD differed by only < 2% from their literature in vivo. The relationship between inhaler orientation and in vitro regional airway deposition was determined. Aerosol drug deposition was found to depend on the angle at which an inhaler is inserted into the mouth although the results for MT deposition were dependent on both the product and the formulation being delivered. In the clinic, inhalation profiles were collected from 20 healthy inhaler naïve volunteers (10M, 10F) before and after they received formal inhalation training in the use of a DPI. Statistically significant improvements in Peak Inhalation Flow Rate (PIFR) and Inhalation Volume (V) were observed following formalized training. The shapes of the average inhalation profiles recorded in the clinic were found to be comparable to the simulated profiles used in the in vitro deposition studies described above. In conclusion, novel in vitro test methods are described that accurately predict both the average and range of aerosol airway drug deposition seen from DPIs in the clinic.

Dry powder inhalers (DPIs) are advantageous for delivering medication to the lungs for the treatment of respiratory diseases because of the stability of the powders, relative low cost, synchronization of inhalation and dose delivery, and many design options that can be used for optimization. However, currently marketed DPIs are very inefficient in delivering medications to the lungs. This study has developed multiple new high efficiency DPIs for use with spray dried excipient enhanced growth (EEG) powder formulations based on the following platforms: capsule-based for oral inhalation, high-dose for oral inhalation, inline with 3D rod array dispersion, and inline with capillary jet dispersion. The capsule-based DPIs for oral inhalation implemented a 3D rod array for aerosol dispersion with optimal designs producing mass median aerodynamic diameters (MMADs) in the range of 1.3-1.5 µm and emitted doses in the range of 79-81%. Keys to inhaler success were the orientation of the capsule and inclusion of the 3D rod array. For the high-dose oral inhaler, performance was similar to the optimized capsule-based devices, while aerosolizing a much larger mass of powder. Surprisingly, removal of the fluidized bed of spheres improved performance producing a simple high dose device containing only a single dose sphere. The inline device using the 3D rod array was effective in producing particles of approximately 1.5 µm, at flow rates consistent with high flow therapy using a 1 L ventilation bag as the delivery mechanism. Using a capillary jet as the dispersion mechanism, further advances were made to allow for both delivery using a low volume (LV) of air and delivery in low flow therapy. This easily adaptable platform was able to produce a high quality aerosol out of a nasal cannula with an ED greater than 60% and a size (~2 µm) that should produce minimal extrathoracic losses. In conclusion, this study demonstrates (i) the design and optimization of DPIs capable of delivering EEG aerosols to the lungs using oral inhalation, (ii) the ability to deliver EEG aerosols using N2L aerosol administration, and (iii) the design of a new flexible LV-DPI device that is easily adaptable to multiple patients and delivery platforms, which are greatly needed in clinical environments.

Managing the respiratory diseases could be hard for many patients. Usually patients use the inhaler to administrate medicine on a regular basis. Even though the inhaler guideline is well-accepted, most patients make mistakes. In the recent years, smart inhalers with sensors have shown a great potential of guiding the daily use of the inhaler and better understanding the diseases. KTH MedTech startup Andning Med AB specializes on developing smart add-on hardware device to the inhaler. This thesis work is the continuation of the prototyping of the embedded software for the add-on device. The main goal of the thesis work is to develop a robust software for the hardware device to guide the inhaler use in real time, and collect and manage the inhaler data. To approach the problem, I use the Finite-state machine modelling and the object-oriented programming mindset. After the software development and testing, all the designed functionalities are achieved. The user could be visually guided by the device. The inhaler data could be correctly collected and uploaded to the mobile device. The thesis work could serve as a basis for further embedded software development for the device that will end up in the smart inhaler market in the future. It could also give reference to the similar IoT device development. / Att hantera luftvägssjukdomarna kan vara svårt för många patienter. Vanligtvis använder patienter inhalatorn för att administrera medicin regelbundet. Även om inhalatorns riktlinje är väl accepterad gör de flesta patienter misstag. Under de senaste åren har smarta inhalatorer med sensorer visat en stor potential att vägleda den dagliga användningen av inhalatorn och bättre förstå sjukdomarna. KTH MedTech startup Andning Med AB har specialiserat sig på att utveckla smarta tilläggsutrustning till inhalatorn. Detta examensarbete är en fortsättning på prototypframställningen av den inbäddade programvaran för tilläggsenheten. Huvudmålet med examensarbetet är att utveckla en robust mjukvara för hårdvaruenheten för att styra inhalatoranvändningen i realtid, samt samla in och hantera inhalatordata. För att närma mig problemet använder jag Finite-state maskinmodellering och det objektorienterade programmeringstänket. Efter mjukvaruutveckling och testning uppnås alla designade funktioner. Användaren kan visuellt guidas av enheten. Inhalatordata kunde samlas in korrekt och laddas upp till den mobila enheten. Examensarbetet kan fungera som en grund för ytterligare inbäddad mjukvaruutveckling för enheten som kommer att hamna på marknaden för smarta inhalatorer i framtiden. Det kan också hänvisa till liknande utveckling av IoT-enheter.

Yes / Two different types of dry powder inhalers (Easyhaler® and RS01®) were used in this work to evaluate the ex vivo and in vitro performance of a budesonide inhaled formulation with recrystallised mannitol, commercial DPI-grade mannitol, or lactose. The aerodynamic performance of the budesonide formulation with recrystallised mannitol was superior when RS01® was used (FPF = 45.8%) compared to Easyhaler® (FPF = 14%). However, the aerodynamic profile was very poor in both devices when commercial mannitol was used. Interestingly, the aerosol performance of the marketed budesonide formulation significantly improved when RS01® was used compared to Easyhaler® (the original device for the formulation). Due to the significant increases in the surface energy of the commercial mannitol formulation, the aerodynamic performance of the formulation was very poor. This work demonstrates the impact of inhaler devices on the performance of inhaled formulations and considers the particle surface energy during formulation development.

Class of 2012 Abstract / Specific Aims: To evaluate the in vitro throat deposition and respirable mass of the QVAR® pressurized metered-dose inhaler (pMDI) alone or coupled to an accessory device, such as the AeroChamber Valved Holding ChamberTM or various nonconventional accessory devices. Methods: The performance of the AeroChamber and nonconventional accessory devices, including a toilet paper roll, paper towel roll, rolled paper, plastic bottle spacer, plastic bottle reverse-flow holding chamber, and nebulizer reservoir tubing, were compared to no accessory device. Throat deposition and respirable mass were evaluated using a United States Pharmacopeia (USP) inlet ("throat") coupled to instrumentation for particle size analysis. Each configuration was tested with three actuations and repeated in quadruplicate. The amount of drug deposition was quantified using high-performance liquid chromatography. The data were analyzed using multiple independent t-tests assuming unequal variances. An a priori α-threshold of 0.05 was used with a Bonferroni corrected α of 0.007. Main Results: Compared to the pMDI alone, all of the accessory devices had significantly lower throat deposition (p < 0.001) and significantly higher respirable fraction (p < 0.001). Differences in respirable mass were not significant for any accessory device (p ≥ 0.049), except the paper towel roll and the nebulizer reservoir tubing (p < 0.001). Conclusions: Under these testing circumstances, nonconventional accessory devices, such as the toilet paper roll, rolled paper, plastic bottle spacer, and plastic bottle reverse-flow holding chamber, effectively reduce throat deposition and maintain respirable mass compared to a QVAR pMDI alone. Therefore, they may be suitable alternatives to commercial spacers.

Candidate active pharmaceutical ingredients (APIs) are routinely tested to determine such parameters as physical stability, chemical stability, and bioavailability. Preformulation analysis of APIs does not currently attemept to determine whether they will perform to an acceptable level once they have been formulated. In practice, the APIs are subjected to extensive in vitro testing of their performance in a formulation, combined with optimisation of the formulation. This formulation testing is both time-consuming and expensive. In the field of pulmonary drug delivery from dry powder inhalers (DPIs), the API has to be aerosolized effectively in order to penetrate the lunfs and reach its deposition target. In a conventional ternary DPI fromulation, the API is combined with carrier lactose and fine lactose particles. The inter-particle forces between these three components and the bulk properties of the formulation determine the structure of the formulation and the aerolization performance of the API. In this study, physicochemical properties of salbutamol base and several of its salts were investigated both quantitatively and qualitatively. The in vitro deposition characteristics of the formulated APIs were also determined. The relationship between these parameters and the deposition was analysed to establish if a rapid preformulation screening technique could be applied to the APIs with respect to predicting the deposition performance of the formulated API. A clear relationship between the deposition of the unformulated API and the formulated API was observed that could be exploited as a screening technique.