Patients in the intensive care unit (ICU) setting are prone to develop muscle weakness and the causes are multi-factorial. Muscle strength in adult, critically ill patients on mechanical ventilation decreases with immobility. The influence of muscle strength on different muscle groups and its influence on progressive mobility in the adult, critically ill patient on mechanical ventilation has not been examined. Identifying muscle strength in this patient population can benefit overall muscle health and minimize muscle deconditioning through a progressive mobility plan. The objective of this dissertation was to describe muscle strength in different muscle groups and to describe the influence of muscle strength on mobility in critically ill adult patients on mechanical ventilation (MV). Fifty ICU patients were enrolled in this descriptive, cross sectional study. Abdominal core, bilateral hand grip and extremity strength was measured using three measurement tools. Mobility was measured using the following scale: 0=lying in bed; 1=sitting on edge of bed; 2=sitting on edge of bed to standing; 3=walking to bedside chair and 4=walking >7 feet from the standing position. Predictors of mobility were examined using stepwise regression. Abdominal core, bilateral hand grip and extremity strength demonstrated statistically significant relationships with all variables. Extremity strength accounted for 82% of the variance in mobility and was the sole predictor (β=0.903; F=212.9; p=0.000). Future research addressing the outcomes of implementing a mobility protocol in this patient population and prioritizing when such a protocol should be implemented would be beneficial to ongoing plans to decrease MV, ICU and hospital days. Muscle strength tests implemented at the bedside are crucial to implementing a progressive mobility plan for critically ill adults while they are on MV therapy.

This descriptive case study examines the use of medical simulation technology in the three-year Thompson Rivers University respiratory therapy training program. Qualitative analysis of data gathered from 78 participants through interviews, observations, and discussion groups reveal a wide variety of low- intermediate- and high-fidelity technologies used for education and evaluation. Deliberate practice is the predominant learning theory informing the use of simulation for safe and ethical training in competencies that would otherwise pose significant risk to patients. Recommendations include enhancements of the existing technology with psychological and environmental fidelity, and for optimal curriculum placement of high-fidelity simulators at hospital sites for student development of critical thinking and team training. Further research into learning with high-fidelity simulation specifically within the context of a student respiratory therapist as an embedded hospital team member is needed. Keywords: respiratory therapy, patient simulation, critical thinking, learning, critical care, deliberate practice

Thesis (M.Sc.)--Memorial University of Newfoundland, Faculty of Medicine, 1998. / Typescript. Bibliography: leaves 118-128.

Background: Clinical instructors are expected to be excellent practitioners with great teaching skills. They play a vital role in teaching the next generation of respiratory therapists (RTs). Because clinical instructors impact the learning process of teaching the next generation, it is important to identify the effective teaching characteristics that contribute to the clinical success of the student from the perspective of RT faculty. PURPOSE: The aim of this study was to identify effective behavioral teaching characteristics of clinical instructors that are deemed most and least important by RT faculty in the State of Georgia. METHODS: Data were collected through a descriptive survey. The survey was adapted and emailed to all RT faculty members listed on The Georgia Society for Respiratory Care (GSRC) website. The survey consisted of three main domains: professional competence, relationship with students, and personal attributes. Thirty-five behavioral teaching characteristics were presented on a five-point Likert scale according to importance. RESULTS: Nineteen responses were received out of forty emailed surveys, with a response rate of 47.5%. The majority of participants indicated a master degree as their highest degree. Almost 58% of the participants teach at programs that offer associate degree. The study findings indicated faculty members’ perceptions ranking of the most important behavioral teaching characteristics hold a lot of similarities and some differences. Among all provided teaching characteristics, “Facilitate critical thinking in clinical practice was perceived as the most important behavioral teaching characteristic with mean scores and S.D of (M 4.89, S.D ±0.31), respectively. In the domain of relationship with students, “Encourage students to feel free to ask questions or ask for help” was ranked the highest by the participants with a mean of 4.57 and S.D of ±0.50. In the personal attributes domain, “Able to collaborate with other disciplines” was ranked as the most important characteristic with mean scores and S.D respectively (M 4.68, S.D ±0.47). CONCULSION: Faculty from different program levels (associate, baccalaureate and master) agreed that “Facilitate critical thinking in clinical practice” was the most important characteristic. Based on these findings, it is highly recommend that clinical instructors strive to improve their attitudes toward students as the best way to achieve the goals of clinical teaching. They also showed the need for respiratory therapy programs to foster and to promote uniformly identified effective behavioral teaching characteristics.

Introdução: A desobstrução rinofaríngea retrógrada (DRR) é uma técnica de fisioterapia respiratória aplicada em lactentes para desobstrução de vias aéreas superiores, podendo, inclusive, ser associada à irrigação nasal com salina isotônica para remoção de muco viscoso aderido às paredes das vias aéreas. Objetivo: Caracterizar o perfil de motociclistas profissionais expostos à poluição urbana no que se refere a transporte mucociliar nasal (TMCN), inflamação das vias aéreas superiores e sintomas nasais, e comparar o efeito da DRR isolada e associada à instilação de salina isotônica (DRR+S) nesta população. Métodos: Vinte e quatro voluntários divididos aleatoriamente em dois grupos (DRR e DRR+S) submeteram-se a 15 dias consecutivos de tratamento. A avaliação basal e a pós-intervenção constituíram-se da análise do teste de trânsito da sacarina, da celularidade total e diferencial do lavado nasal e dos sintomas de vias aéreas superiores por meio do questionário SNOT-20, bem como do estudo da exposição pessoal à poluição do ar, por meio da análise da concentração do NO2 de amostradores passivos. O TMCN foi avaliado pelo teste ANOVA não paramétrico com medidas repetidas e o SNOT-20 pelo teste Mann-Whitney. As correlações entre a concentração de NO2 e os desfechos das vias aéreas superiores foram testadas por meio do coeficiente de correlação de Spearman. Resultados: Os grupos apresentaram dados clínicos e demográficos semelhantes. O TMCN apresentou-se alterado em 25% dos voluntários e 100% deles apresentavam sintomas de vias aéreas superiores. Após os tratamentos, os sintomas de vias aéreas e o TMCN evidenciaram melhora significativa, apesar do aumento no número de macrófagos e células ciliadas do lavado nasal. Não houve correlação entre o NO2 e o TMCN, tampouco em relação aos sintomas de vias aéreas superiores. CONCLUSÃO: Técnicas não farmacológicas, simples e de baixo custo são efetivas para recuperar o TMCN alterado e melhorar os sintomas de vias aéreas superiores em adultos não tabagistas / Introduction: Rhinopharyngeal Retrograde Clearance (RRC) is a respiratory therapy technique applied to infants with upper airway obstruction that may also be associated with nasal irrigation with isotonic saline for removal of viscous mucus adhered to the walls of the airways. OBJECTIVE: Characterize the profile of professional motorcycles exposed to urban pollution in relation to the nasal mucociliary transport (NMCT), inflammation of the upper airways and nasal symptoms and compare the effect of DRR alone and associated with instillation of isotonic saline (RCC + S). Methods: Twenty-four volunteers were randomly divided into two groups (RCC and RCC + S) and were submitted to 15 consecutive days of treatment. The baseline and post-intervention consisted of analysis of the transit saccharin test, the total and differential cellularity nasal lavage, and symptoms of upper airway through the SNOT-20, as well as the study of personal exposure to air pollution, by analyzing the concentration of diffuse nitrogen dioxide monitoring system. The NMCT was evaluated with ANOVA for repeated measures and the SNOT-20 with the Mann-Whitney test. The correlations between the concentration of NO2 and the upper airway outcomes were tested using the Spearman correlation coefficient. Results: The groups showed similar demographic and clinical data. The NMCT was abnormal in 25% of the volunteers and 100% of the volunteers had symptoms of upper airways. After treatment the upper airway symptoms and the NMCT showed significant improvement despite the increase in the number of macrophages and ciliated cells on the nasal lavage. No correlation was observed between dioxide nitrogen and TMCN and with the symptoms of the upper airways. Conclusion: Nonpharmacological, simple and inexpensive techniques are effective to treat abnormal NMCT and improve symptoms of upper airway in nonsmoking adults

An evidence-based approach to clinical practice aims to deliver appropriate care in an efficient manner to individual patients. This approach entails the integration of research evidence, clinical expertise and the interpretation of patients' needs and perspectives in making decisions about the best care modalities. The increased emphasis internationally on improved patient care and cost effectiveness in health care delivery highlighted the need for quality health services that have to be built upon the use of best evidence to inform practice and patient-care decision-making (McKenna, Ashton and Keeney, 2004:178). Critical care nursing science, a specialised branch of nursing, focusing on the care of the critically ill patient in a designated unit, is no exception to the drive to provide improved quality and cost-effective patient care. Critical care practitioners are seen to have a specialised knowledge base, specific skills in delivering advanced health care and a commitment to serve the critically ill patient. It is expected of them to be aware of new and emerging evidence about health disease processes, treatment modalities and technology used in the critical-care units. Due to the dynamic nature of a critical care unit, it is essential that every practitioner working in the unit, whether a novice professional nurse or senior unit manager, needs to be aware of the current evidence guiding their practices (Elliot, Aitken, Chaboyer, 2007:18). With reference to the critically ill patient who is connected to a mechanical ventilator, practices related to the nursing care of this group of patients, who mostly occupy the critical care units, should be based on the best evidence in order to provide cost-effective and quality care. The research study aimed to explore and describe four identified nursing care practices related to safety of a mechanically ventilated patient as performed by professional nurses in the critical care units in the Nelson Mandela Metropole. The identified nursing-care practices include: endotrachael tube placement verification, endotracheal tube cuff pressure monitoring, endotrachael tube suctioning and mechanical ventilator settings. This objective was operationalized in Stage One of the study, by using a quantitative, explorative, descriptive and contextual approach. A structured questionnaire was utilised to collect data from professional nurses working in critical care units. From the analysed data, it was decided to select the two nursing care practices that were done least according to the best recommended practice, namely endotracheal tube suctioning and endotracheal tube cuff pressure monitoring. Based on the results, systematic reviews were done respectively on the two nursing care practices. On completion of Stage One of the study, evidence-informed clinical guidelines for the two identified nursing care practices were developed. The clinical guidelines were based on the evidence found in conducting the systematic reviews. The draft clinical guidelines were reviewed by an expert panel. Feedback from the reviewers was considered to prepare the final evidence-informed clinical guidelines. Based on the clinical guidelines, two clinical algorithms were developed, which might be used at the patient's bedside and can assist in quick dissemination of the recommendations for practice. Ethical considerations were maintained throughout the study. The quality of the study was ensured in applying the principles of validity and reliability as well as performing a critical appraisal of all data collected during the systematic review. It is envisaged that the study findings be disseminated in the critical care units in the Nelson Mandela Metropole and published in peer reviewed journals.

A lesão nasal decorrente do uso da ventilação não invasiva (VNI) é um evento adverso cada vez mais comum nas unidades de terapia intensiva neonatais (UTIN) e apresenta consequências a curto e longo prazo. Esta lesão pode resultar em sequelas tanto de ordem estética quanto funcional, limitar o uso da VNI em RN que necessita desse suporte ventilatório, causar desconforto e septicemia; podendo aumentar, desta forma, o tempo de internamento na UTIN. Esta pesquisa tem por objetivo avaliar tecnológica e clinicamente os protetores nasais empregados na VNI de RN internados na UTIN. A metodologia consistiu primeiramente em levantar as possíveis causas da lesão nasal e avaliar os fatores de risco associados ao seu desenvolvimento. Em seguida, foi realizado um ensaio clínico randomizado para comparar os efeitos de três tipos de proteção nasal e das prongas novas e esterilizadas sobre a gravidade da lesão nasal. E por fim, foi realizada a caracterização térmica e estrutural dos protetores nasais após serem envelhecidas com temperatura e umidade no interior da incubadora neonatal. As principais causas da lesão foram relacionadas às características do material, a problemas no equipamento, a fatores assistenciais, neonatais e profissionais. Neste estudo, foram constatados como fatores de risco: a idade gestacional, a massa ao nascer, o tempo total de permanência na VNI, a reutilização deste suporte, o tempo da primeira utilização e da reutilização da VNI, bem como o tempo de internação na UTIN. Não foram observadas diferenças significativas na gravidade da lesão quando comparadas as três proteções estudadas, nem quando utilizadas prongas novas e esterilizadas. Quanto à análise dos materiais, foi constatado que a exposição à temperatura e à umidade alterou a percentagem de cristalinidade e a rugosidade das proteções nasais estudadas. / The nasal injury resulting from the use of non-invasive ventilation (NIV) is an adverse event increasingly common in the newborn intensive care unit (NICU) and shows the short and long term consequences. This lesion can result both aesthetic and functional sequelae, limit the use of NIV in newborns who need this ventilatory support, cause discomfort and septicemia, may thereby increase the length of stay in NICU. This research aims to evaluate technological and clinically nasal protectors used with NIV of newborns admitted to the NICU. The methodology consisted primarily in raising the possible causes of nasal injury and assess the risk factors associated with its development. Then, it was conducted a randomized clinical trial to compare the effects of three kind of nasal protector and new and sterilized prongs on the severity of nasal lesions. And finally, it was performed the thermal and structural characterization of nasal protection after being aged with temperature and humidity inside the neonatal incubator. The main causes of injury were related to characteristics of the material, equipment problems, assistive, neonatal and professional factors. In this study, it was found as risk factors: gestational age, weight at birth, the total time stay in the NIV, the reuse of this support, the time of first use and reuse of NIV and the length of stay in the NICU. They were not observed significant differences in lesion severity when compared the three protectors studied, nor when used new and sterilized prongs. The materials analysis indicated that exposure to temperature and humidity changed the percentage of crystallinity and the roughness of the nasal protections studied.

A lesão nasal decorrente do uso da ventilação não invasiva (VNI) é um evento adverso cada vez mais comum nas unidades de terapia intensiva neonatais (UTIN) e apresenta consequências a curto e longo prazo. Esta lesão pode resultar em sequelas tanto de ordem estética quanto funcional, limitar o uso da VNI em RN que necessita desse suporte ventilatório, causar desconforto e septicemia; podendo aumentar, desta forma, o tempo de internamento na UTIN. Esta pesquisa tem por objetivo avaliar tecnológica e clinicamente os protetores nasais empregados na VNI de RN internados na UTIN. A metodologia consistiu primeiramente em levantar as possíveis causas da lesão nasal e avaliar os fatores de risco associados ao seu desenvolvimento. Em seguida, foi realizado um ensaio clínico randomizado para comparar os efeitos de três tipos de proteção nasal e das prongas novas e esterilizadas sobre a gravidade da lesão nasal. E por fim, foi realizada a caracterização térmica e estrutural dos protetores nasais após serem envelhecidas com temperatura e umidade no interior da incubadora neonatal. As principais causas da lesão foram relacionadas às características do material, a problemas no equipamento, a fatores assistenciais, neonatais e profissionais. Neste estudo, foram constatados como fatores de risco: a idade gestacional, a massa ao nascer, o tempo total de permanência na VNI, a reutilização deste suporte, o tempo da primeira utilização e da reutilização da VNI, bem como o tempo de internação na UTIN. Não foram observadas diferenças significativas na gravidade da lesão quando comparadas as três proteções estudadas, nem quando utilizadas prongas novas e esterilizadas. Quanto à análise dos materiais, foi constatado que a exposição à temperatura e à umidade alterou a percentagem de cristalinidade e a rugosidade das proteções nasais estudadas. / The nasal injury resulting from the use of non-invasive ventilation (NIV) is an adverse event increasingly common in the newborn intensive care unit (NICU) and shows the short and long term consequences. This lesion can result both aesthetic and functional sequelae, limit the use of NIV in newborns who need this ventilatory support, cause discomfort and septicemia, may thereby increase the length of stay in NICU. This research aims to evaluate technological and clinically nasal protectors used with NIV of newborns admitted to the NICU. The methodology consisted primarily in raising the possible causes of nasal injury and assess the risk factors associated with its development. Then, it was conducted a randomized clinical trial to compare the effects of three kind of nasal protector and new and sterilized prongs on the severity of nasal lesions. And finally, it was performed the thermal and structural characterization of nasal protection after being aged with temperature and humidity inside the neonatal incubator. The main causes of injury were related to characteristics of the material, equipment problems, assistive, neonatal and professional factors. In this study, it was found as risk factors: gestational age, weight at birth, the total time stay in the NIV, the reuse of this support, the time of first use and reuse of NIV and the length of stay in the NICU. They were not observed significant differences in lesion severity when compared the three protectors studied, nor when used new and sterilized prongs. The materials analysis indicated that exposure to temperature and humidity changed the percentage of crystallinity and the roughness of the nasal protections studied.

Title Best current evidence on chest physiotherapy in non-ventilated paediatric patients (0 to 24 months) with bronchiolitis: a systematic review. Purpose To determine the current scientific evidence for using three chest physiotherapy modalities namely percussion, postural drainage and suctioning in paediatric patients (0 to 24 months). Relevance The field of cardiopulmonary physiotherapy seems to be a neglected area in physiotherapy, with a subsequently limited evidence base. The author observed that in various clinical settings physiotherapists tend to administer routine chest physiotherapy to paediatric patients with bronchiolitis. Findings from this study may assist physiotherapists in their choice of effective treatment options. Sources The following databases were searched for evidence: African Health Line, CINAHL, Cochrane, Ebsco Host, Emerald Host, UP E-theses/dissertations, PEDro, Medline Ovid, Sabinet, Science Direct, Up To Date. Methodology This was a systematic review. The databases were reviewed by making use of a specified search strategy customised for each database. Keywords were: physiotherapy/physical therapy, bronchiolitis and paediatric/pediatric in combination with percussion, postural drainage and suction. The search yielded 10,016 study titles. Studies were chosen from the population of studies using pre-set inclusion and exclusion criteria. These criteria were applied to the titles, abstracts and full-text articles as appropriate. Five full text-articles were appraised and based on the scores from the appraisal three were included in the final sample. Data analysis Appraisal instruments from the National Health System Critical Appraisal Skills Programme (NHS CASP) and the PEDro scale (for randomised controlled trials) were used to evaluate and score the sample. Scoring was done independently by two researchers, and agreement reached through negotiation. The evidence was synthesised and graded according to the Sackett hierarchy of evidence. Results Owing to the heterogeneity of the sample, and the nature of results reported, a meta-analysis was not possible. Results from this study reveal that there is no evidence to support routine chest physiotherapy in uncomplicated viral bronchiolitis amongst the paediatric population. Chest physiotherapy does not decrease length of hospital stay, oxygen requirements or clinical scores indicating distress/morbidity. However, with secondary bacterial respiratory infections, chest physiotherapy may be indicated, depending on the assessment of each individual patient. Conclusion Percussion, postural drainage and suctioning are not effective in the management of bronchiolitis in children, newborn to 24 months old, except in individually assessed cases with secondary bacterial infection. In this subset, physiotherapy must be customised to the patient. Therefore routine physiotherapy is not indicated. Implications Chest physiotherapy should be based on a complete evaluation and on clinical merit, as well as on evidence and patient preference. Education of physiotherapy students at universities as well as doctors regarding the current evidence for chest physiotherapy in paediatric bronchiolitis is essential. Doctors and clinicians need to be made aware that routine chest physiotherapy for paediatric patients with bronchiolitis should not be prescribed. AFRIKAANS : Titel Die beste huidige bewyse aangaande longfistioterapie vir non geventileerde pediatriese pasiënte (0 tot 24 maande) met brongiolitis: 'n sistematiese oorsig. Doel Om huidige wetenskaplike bewyse vir die gebruik van drie long fisioterapietegnieke naamlik beklopping, posturale dreinasie en suiging in pediatriese pasiënte (0 tot 24 maande) te bepaal. Toepaslikheid Die veld van pediatriese fisioterapie blyk 'n verwaarloosde area van navorsing te wees, met gevolglik beperkte bewysbasis. Die navorser het ondervind dat fisioterapeute dikwels in kliniese praktyk roetine longfisioterapie in pediatriese pasiënte met brongiolitis toepas. Bewyslewering vanuit hierdie studie kan fisioterapeute help met die keuse van effektiewe behandelingsprosedures. Bronne Die volgende databasisse is deursoek vir bewyse: African Health Line, CINAHL, Cochrane, Ebsco Host, Emerald Host, UP e-theses and dissertations, PEDro, Medline, Sabinet, Science Direct en Up To Date. Die soektog het 10,016 titels gelewer. Metode 'n Sistematiese oorsig van die data is uitgevoer deur 'n gespesifiseerde soekstrategie, aangepas vir elke databasis, te volg. Sleutelwoorde was: “physiotherapy/physical therapy”, “bronchiolitis” and “paediatric/pediatric” in kombinasie met “percussion”, “postural drainage” and “suction”. Voorafbepaalde insluitings- en uitsluitingskriteria is toegepas op titels, abstrakte en artikels soos toepaslik. Data analise Evalueringsinstrumente van die “National Health System Critical Appraisal Skills programme” (NHS CASP) asook die PEDro skaal (ewekansige gekontroleerde eksperiment) is gebruik vir evaluasie van en puntetoedeling vir die verkose studies. Die puntetoekenning is onafhanklik deur twee navorsers gedoen en konsensus is bereik deur onderhandeling. Die inligting verkry is gesintetiseer en gegradeer aan die hand van die Sackett hiërargie van bewyse. As gevolg van die heterogeniteit van die ingeslote studies en die aard van die resultate was 'n meta-analise nie moontlik nie. Resultate Die studie het bevind dat daar geen bewyse is vir roetine borskasfisioterapie van ongekompliseerde akute virale pediatriese brongiolitis nie. Borskasfisioterapie verminder nie die duur van hospitaalverblyf, suurstofbehoeftes of die kliniese respiratoriese aanduiding van stres in die pasiënte nie. In die geval van sekondêre bakteriële respiratoriese infeksies mag borskasfisoterapie egter geindikeerd wees, afhangend van die evaluasie van elke individuele pasiënt. Gevolgtrekking Beklopping, posturale dreinasie, en suiging as roetine behandeling is nie effektief in die behandeling van brongiolitis in pasgebore tot 24 maand oue pasiënte nie, behalwe individuele gevalle met sekondêre bakteriële infeksies. In hierdie spesifieke subgroep moet borskasfisioterapie aangepas word vir pasiënt. Roetine fisioterapie is dus nie aangedui nie. Implikasies Borskasfisioterapie moet gebasseer wees op 'n volledige evaluasie en kliniese meriete, asook bewyslewering en die pasiënt se voorkeure. Opleiding van fisioterapie studente by universiteite, asook dokters aangaande die huidige bewyslewering vir borskasfisioterapie in pediatriese brongiolitis is belangrik. Dokters en klinici moet bewus gemaak word dat roetine borskasfisioterapie vir pediatriese brongiolitis pasiënte nie voorgeskryf moet word nie. Additional information available on a CD stored at the Merensky Library. / Dissertation (MPhysT)--University of Pretoria, 2011. / Physiotherapy / unrestricted

Local delivery of medication to the lung is highly desirable as the principal advantages include reduced systemic side effects and higher dose levels of the applicable medication at the site of drug action. This administration could be particularly useful for patients with specifically chronic pulmonary infections or pulmonary diseases, such as cystic fibrosis, asthma or lung cancer.<p>In order to deliver a high dose range of medication for highly-dosed drugs such as antibiotics, “carrier-free” DPI formulations of tobramycin were developed with the aim of minimizing the use of excipients. Briefly, dry powders were prepared by spray drying various suspensions of tobramycin in isopropanol.<p><p>First, as particle size is a key parameter in defining drug deposition in the lungs, the new Spraytec® laser diffraction method specifically modified for measuring the PSD of aerosolized drug was evaluated. The dispersion properties of various dry powder formulations were investigated using different laser diffraction and impaction apparatuses at different flow rates and using different inhalator devices. Different correlations between geometric and aerodynamic size data were demonstrated in this study. As a potential application, for the flow rate, the different inhalation devices and the drug formulations examined, the tobramycin fine particle fraction could be predicted from measurements obtained from the Spraytec® using linear relationships. Correlations (R² > 0.9) between the MMAD and the percentage of particles with a diameter below 5 µm could be demonstrated between the results obtained from the laser diffraction technique and the impaction method. Consequently, the Spraytec® laser diffraction technique was proved to be an important tool for initial formulation and process screening during formulation development of DPIs.<p><p>In order to modify the surface properties of the raw tobramycin powder, different powder compositions were formulated with the aim of studying the influence of the concentration of tobramycin in drug suspensions used for spray-drying, the lipid film composition (cholesterol:Phospholipon ratio) and the coating level (in percentage) on the physicochemical and aerodynamic characteristics of the antibiotic.<p>The results indicated that the application of a lipid coating around the active particles allowed an improvement in particle dispersion from the inhalator, decreasing raw powder agglomeration and thus enhancing drug deposition deep in the lungs. Moreover, these results seemed to be influenced by the amount and composition of the lipids in the formulations. The evaluation of the influence of the coating level showed that the deposition of only 5% w/w lipids (on a dry basis) was sufficient to improve particle dispersion properties during inhalation. The FPF, which is around 36% for the uncoated micronized tobramycin, was increased to up to about 68% for the most effective lipid-coated formulation. Of particular importance, these results revealed the need to add sufficient amounts of covering material in order to significantly modify the particle surface properties and reduce their tendency to agglomeration, while limiting the lipid level in the formulations in order to avoid any undesirable sticking and to allow the delivery of more of the active drug to the deep lung. <p><p>Another approach used to modify the surface properties of raw tobramycin was to coat the micronized particles with nanoparticles of the drug, produced by high pressure homogenization. The evaluation of the influence of the level of nanoparticle coating of the micronized particles showed that the presence of nanoparticles in the formulations improved the particle dispersion properties during inhalation. One microparticle was completely covered with a single layer or several layers of nanoparticles, in function of the percentage of nanoparticles in the mixture. Coating the fine drug particles with particles in the nanometer range was believed to reduce Van Der Waals forces and powder agglomeration. These various layers of nanoparticles also allowed a decrease in the cohesion of the powder by improving the slip between the particles.<p>On the other hand, suspensions containing solely nanoparticles were spray dried with various concentrations of surfactant in order to produce easily dispersible and reproducible micron-size agglomerates of nanoparticles during inhalation. The evaluation of the influence of the concentration of surfactant showed that deposition of only 2% w/w (on a dry basis) of Na glycocholate is sufficient to improve particle dispersion properties during inhalation. Consequently, the use of nanoparticles in dry powder formulations increased the FPF from 36% for the uncoated micronized tobramycin to about 61% for this latter formulation.<p>To modify the balance between the different forces of interactions without the need for any excipient, the influence of formulation components on the aerosolization characteristics of spray-dried tobramycin through the use of various proportions of water in the solvent used to prepare initial suspensions was investigated. These results showed that it is possible to modify the surface properties of the particles by coating the particles of drug with a homogeneously distributed film of the active compound dissolved in a solvent system containing a mixture of different solvents such as isopropanol and water. During nebulization of the suspension, droplets are composed of one or more particles in solid state surrounded with solvent containing the dissolved drug. It is hypothesized that during the drying step, dissolved tobramycin forms a coating of the amorphous drug around particles in suspension. The coating of drug particles can thus be used as an alternative approach that permits the modification of the surface properties of the particles, increasing the flowability, the desagglomeration tendency and the fine particle fraction deposited in the deep lung. So, the evaluation of the influence of the water content of the suspensions and the effect of the inlet temperature during spray-drying showed that the addition of 2% water v/v is sufficient to improve particle dispersion during inhalation. Of particular interest, as tobramycin is a very hygroscopic drug, the addition of water turned out to be a critical step. It was thus important to add a small amount of water to the solvent system and to process the drying step at a high temperature to produce formulations containing solely the active drug and showing a FPF of up to 50%.<p><p>Moreover, stability studies demonstrated that these optimized formulations (lipid-coated formulation, nanoparticle formulation and amorphous drug-coated formulation) were stable over a long time period at various ICH temperature and relative humidity storage conditions (25°C/60% RH, 30°C/65% RH and 40°C/75% RH). The formulations were shown to keep their crystalline state, initial PSD, redispersion characteristics and deposition results for more than twelve months.<p><p>In order to confirm these encouraging results, two optimized formulations (one with a lipid coating and another with amorphous drug coating) were selected and compared to the only commercially available tobramycin formulation for inhalation, Tobi® (nebulizer solution), by performing a combined in vivo scintigraphic and pharmacokinetic evaluation of tobramycin DPIs in nine CF patients.<p>In comparison with Tobi®, it was estimated that lung deposition, expressed as a percentage of the nominal dose, was 7.0 and 4.5 times higher for the lipid-coated and amorphous tobramycin-coated formulations, respectively. Moreover, the pharmacokinetic data, adjusted to the same drug dose as that of the Tobi® deposited in the lungs, showed that the AUC values were found to be 1.6 times higher for Tobi® than for DPI formulations. So this evaluation confirmed the superiority of dry powder formulations in terms of drug deposition and reduced systemic exposure in comparison with the conventional comparator product, Tobi®.<p><p>Thus, these new and orginal tobramycin DPI formulations based on the use of very low excipient levels and presenting very high lung deposition properties, were shown to offer very good prospects for improving the delivery of drugs to the pulmonary tract and to the widest possible patient population. <p><p> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished