Optimization of an in vitro method for assessing pulmonary permeability of inhaled drugs using alveolar epithelial cells.

INTRODUCTION: Inhalation of drugs for the treatment of pulmonary diseases has been used since a long time. Due to lungs' larger absorptive surface area, delivery of drugs to the lungs is the method of choice for different disorders. Here we present the establishment of a comprehensive permeability model using Type II alveolar epithelial cells and Beclomethasone Dipropionate (BDP) as a model drug delivered by pressurized metered dose inhaler (pMDI). METHODS: Using Type II alveolar epithelial cells, the method was standardized for parameters viz., cell density, viability, incubation period and membrane integrity. The delivery and deposition of drug were using the pMDI device with a Twin Stage Impinger (TSI) modified to accommodate cell culture insert having monolayer of cells. The analytical method for simultaneous estimation of BDP and Beclomathasone-17-Monopropionate (17-BMP) was validated as per the bioanalytical guidelines. The extent and rate of absorption of BDP was determined by quantifying the amount of drug permeated and the data represented by calculating its apparent permeability. RESULTS: Type II alveolar epithelial cells cultured at 0.55 × 105 cells/cm2 for 8-12 days under air-liquid interface were optimized for conducting permeability studies. The data obtained for absorptive transport showed a linear increase in the drug permeated against time for both BDP and 17-BMP along with proportional permeability profile. DISCUSSION: We have developed a robust in vitro model to study absorptive rate of drug transport across alveolar layer. Such models would create potential value during formulation development for comparative studies and selection of clinical candidates.

Salbutamol Easyhaler provides non-inferior relief of methacholine induced bronchoconstriction in comparison to Ventoline Evohaler with spacer: A randomized trial.

BACKGROUND: Salbutamol is a cornerstone for relieving acute asthma symptoms, typically administered through a pressurized metered-dose inhaler (pMDI). Dry powder inhalers (DPIs) offer an alternative, but concerns exist whether DPIs provide an effective relief during an obstructive event. OBJECTIVE: We aimed to show non-inferiority of Salbutamol Easyhaler DPI compared to pMDI with spacer in treating methacholine-induced bronchoconstriction. Applicability of Budesonide-formoterol Easyhaler DPI as a reliever was also assessed. METHODS: This was a randomized, parallel-group trial in subjects sent to methacholine challenge (MC) test for asthma diagnostics. Participants with at least 20 % decrease in forced expiratory volume in 1 s (FEV1) were randomized to receive Salbutamol Easyhaler (2 × 200 µg), Ventoline Evohaler with spacer (4 × 100 µg) or Budesonide-formoterol Easyhaler (2 × 160/4.5 µg) as a reliever. The treatment was repeated if FEV1 did not recover to at least -10 % of baseline. RESULTS: 180 participants (69 % females, mean age 46 yrs [range 18-80], FEV1%pred 89.5 [62-142] %) completed the trial. Salbutamol Easyhaler was non-inferior to pMDI with spacer in acute relief of bronchoconstriction showing a -0.083 (95 % LCL -0.146) L FEV1 difference after the first dose and -0.032 (-0.071) L after the last dose. The differences in FEV1 between Budesonide-formoterol Easyhaler and Salbutamol pMDI with spacer were -0.163 (-0.225) L after the first and -0.092 (-0.131) L after the last dose. CONCLUSION: The study confirms non-inferiority of Salbutamol Easyhaler to Ventoline Evohaler with spacer in relieving acute bronchoconstriction, making Easyhaler a sustainable and safe reliever for MC test and supports its use during asthma attacks.

On the Feasibility of Rugose Lipid Microparticles in Pressurized Metered Dose Inhalers with Established and New Propellants.

Pressurized metered dose inhalers (pMDIs) require optimized formulations to provide stable, consistent lung delivery. This study investigates the feasibility of novel rugose lipid particles (RLPs) as potential drug carriers in pMDI formulations. The physical stability of RLPs was assessed in three different propellants: the established HFA-134a and HFA-227ea and the new low global-warming-potential (GWP) propellant HFO-1234ze. A feedstock containing DSPC and calcium chloride was prepared without pore forming agent to spray dry two RLP batches at inlet temperatures of 55 °C (RLP55) and 75 °C (RLP75). RLPs performance in pMDI formulations was compared to two reference samples that exhibit significantly different performance when suspended in propellants: well-established engineered porous particles and particles containing 80% trehalose and 20% leucine (80T20L). An accelerated stability study at 40 °C and relative humidity of 7% ± 5% was conducted over 3 months. At different time points, a shadowgraphic imaging technique was used to evaluate the colloidal stability of particles in pMDIs. Field emission electron microscopy with energy dispersive X-ray spectroscopy was used to evaluate the morphology and elemental composition of particles extracted from the pMDIs. After 2 weeks, all 80T20L formulations rapidly aggregated upon agitation and exhibited significantly inferior colloidal stability compared to the other samples. In comparison, both the RLP55 and RLP75 formulations, regardless of the propellant used, retained their rugose structure and demonstrated excellent suspension stability comparable with the engineered porous particles. The studied RLPs demonstrate great potential for use in pMDI formulations with HFA propellants and the next-generation low-GWP propellant HFO-1234ze.

Environmentally sustainable opportunities for health systems: metered-dose inhaler prescribing, dispensing, usage, and waste at The Ottawa Hospital.

BACKGROUND: The carbon footprint of Canada's health sector is among the worst in the world, responsible for 4·6% of Canada's total greenhouse gas emissions. A quarter of emissions from Canada's health sector are linked to pharmaceuticals, including metered dose inhalers (MDIs). MDIs use propellants, such as hydrofluorocarbons, which act as greenhouse gas emissions and contribute to the health-care sector's overall carbon footprint. The objective of this study was to describe MDI prescribing, dispensing, usage, and waste patterns at The Ottawa Hospital (Ottawa, ON, Canada). Secondary objectives included estimating the monetary and carbon cost of current practice and the potential benefits and costs of switching to the more environmentally friendly dry powder inhalers. METHODS: In this retrospective point-prevalence cohort study, we identified 100 consecutive patients from medical and surgical services at both campuses of The Ottawa Hospital from health records discharged from medical and surgical services and who were prescribed at least one MDI during their admission. Medical records were reviewed and data related to demographics, MDI prescribing, dispensing, usage, and wastage were collected using a pre-piloted electronic case report form. Financial cost was calculated using local costing estimates and carbon cost was calculated using published estimates. FINDINGS: Between Jan 1, 2023, and June 1, 2023, we collected data for 100 eligible patients, of whom 60 (60%) were female and 90 (90%) were admitted to hospital medicine wards (10% from surgical wards). The median length of stay was 7 (range 1-47) days. The most common inpatient diagnoses were respiratory tract infections in 43 (43%) of 100 patients and chronic obstructive pulmonary disease exacerbations in 28 (28%) of 100 patients. The median number of MDIs prescribed during a patients stay was two (range one to 15) and the median number dispensed was one (range one to seven). For formulary options of MDIs, of the 200 (range 30-1400) actuations dispensed per patient, 8% were used, representing 92% wastage. During the audit, 315 MDIs were dispensed in total, of which 97 were not used at all. INTERPRETATION: MDIs are significant contributors to the carbon footprint attributed to pharmaceutical use in hospitals. This study suggests that 90% of MDI doses are wasted, showing that there is substantial room for improvement. FUNDING: None.

Optimal Inhalation Profile of Pressurized Metered Dry Powder Inhaler Using a Valved Holding Chamber: A Dynamic Analysis.

Background: The combined use of a pressurized metered-dose inhaler and valved holding chamber (pMDI+VHC) is recommended to improve efficiency and safety; however, aerosol release is likely to vary with the inhalation maneuver. This in vitro study investigated the aerodynamic characteristics and aerosol release features of pMDI+VHC (Aerochamber, Trudell Medical International). Methods: The static and dynamic changes in the airway resistance (Raw) during inhalation (withdrawal) through pMDI+VHC were measured. Subsequently, the aerosol released from pMDI+VHC was measured using simplified laser photometry during withdrawal with either fast ramp-up then steady or slow ramp-up followed by gradual decrement at different intensities and times to peak flow (TPWF). Results: Raw increased linearly with changes in the withdrawal flow (WF) rate between 10 and 50 L/min. The slope was steep in the low WF range (<50 L/min) and became milder in the higher range. The aerosol mass tended to increase with an increase in the peak WF (PWF) of slow ramp-up profile. When three different WF increment slopes (TPWF: 0.4, 1.4, and 2.4 seconds) were compared, the released aerosol mass tended to decrease, and the aerosol release time was prolonged at longer TPWF. When the PWF was increased, the aerosol release time became shorter, and the withdrawn volume required for 95% aerosol release became larger; however, it did not exceed 0.4 L at suitable TPWF (0.4 seconds). Conclusion: Raw analysis suggests that inhalation at 30-50 L/min is suitable for pMDI+VHC in this setting. Rapid (TPWF, 0.4 seconds) inhalation, but not necessarily long (maximum 2.0 seconds) and deep (but larger than 0.55 L), is also recommended. Practically, direct inhalation to be weaker than usual breathing, as fast as possible, and far less than 2.0 seconds.

The carbon footprint of as-needed budesonide/formoterol in mild asthma: a post hoc analysis.

INTRODUCTION: The use of pressurised metered-dose inhalers (pMDIs) and asthma exacerbations necessitating healthcare reviews contribute substantially to the global carbon footprint of healthcare. It is possible that a reduction in carbon footprint could be achieved by switching patients with mild asthma from salbutamol pMDI reliever-based therapy to inhaled corticosteroid-formoterol dry powder inhaler (DPI) reliever therapy, as recommended by the Global Initiative for Asthma. METHODS: This post hoc analysis included all 668 adult participants in the Novel START trial, who were randomised 1:1:1 to treatment with as-needed budesonide/formoterol DPI, as-needed salbutamol pMDI or maintenance budesonide DPI plus as-needed salbutamol pMDI. The primary outcome was carbon footprint of asthma management, expressed as kilograms of carbon dioxide equivalent emissions (kgCO2e) per person-year. Secondary outcomes explored the effect of baseline symptom control and adherence (maintenance budesonide DPI arm only) on carbon footprint. RESULTS: As-needed budesonide/formoterol DPI was associated with 95.8% and 93.6% lower carbon footprint compared with as-needed salbutamol pMDI (least-squares mean 1.1 versus 26.2 kgCO2e; difference -25.0, 95% CI -29.7 to -20.4; p<0.001) and maintenance budesonide DPI plus as-needed salbutamol pMDI (least-squares mean 1.1 versus 17.3 kgCO2e; difference -16.2, 95% CI -20.9 to -11.6; p<0.001), respectively. There was no statistically significant evidence that treatment differences in carbon footprint depended on baseline symptom control or adherence in the maintenance budesonide DPI arm. CONCLUSIONS: The as-needed budesonide/formoterol DPI treatment option was associated with a markedly lower carbon footprint than as-needed salbutamol pMDI and maintenance budesonide DPI plus as-needed salbutamol pMDI.

Evaluating the pharmacokinetics of beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide delivered via pressurised metered-dose inhaler using a low global warming potential propellant.

INTRODUCTION: Use of propellants with high global warming potential (such as HFA-134a) for pressurised metered-dose inhalers (pMDIs) is being phased down. Switching to dry-powder inhalers may not be clinically feasible for all patients; an alternative is reformulation using propellants with low global warming potential. The combination of beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB) is available for asthma or chronic obstructive pulmonary disease via pMDI using HFA-134a as propellant. This is being reformulated using the low global warming potential propellant HFA-152a. This manuscript reports three studies comparing BDP/FF/GB pharmacokinetics delivered via pMDI using HFA-152a vs HFA-134a. METHODS: The studies were four-way crossover, single-dose, randomised, double-blind, in healthy volunteers. In Studies 1 and 2, subjects inhaled four puffs of BDP/FF/GB (Study 1: 100/6/12.5 µg [medium-strength BDP]; Study 2: 200/6/12.5 µg [high-strength]), ingesting activated charcoal in two of the periods (once per propellant). In Study 3, subjects inhaled medium- and high-strength BDP/FF/GB using a spacer. All three studies compared HFA-152a vs HFA-134a in terms of lung availability and total systemic exposure of beclometasone-17-monopropionate (B17MP; active metabolite of BDP), BDP, formoterol and GB. Bioequivalence was concluded if the 90 % confidence intervals (CIs) of the ratios between formulations of the geometric mean maximum plasma concentration (Cmax) and area under the plasma concentration-time curve between time zero and the last quantifiable timepoint (AUC0-t) for the analytes were between 80 and 125 %. RESULTS: In Studies 1 and 2, systemic exposure bioequivalence (i.e., comparisons without charcoal block) was demonstrated, except for GB Cmax in Study 2 (upper 90 % CI 125.11 %). For lung availability (i.e., comparisons with charcoal block), B17MP and formoterol demonstrated bioequivalence in both studies, as did BDP in Study 2; in Study 1, BDP upper CIs were 126.96 % for Cmax and 127.34 % for AUC0-t). In Study 1, GB AUC0-t lower CI was 74.54 %; in Study 2 upper limits were 135.64 % for Cmax and 129.12 % for AUC0-t. In Study 3, the bioequivalence criteria were met for BDP, B17MP and formoterol with both BDP/FF/GB strengths, and were met for GB AUC0-t, although not for Cmax. Both formulations were similarly well tolerated in all three studies. CONCLUSIONS: Overall, while formal bioequivalence cannot be concluded for all analytes, these data suggest therapeutic equivalence of the new formulation with the existing BDP/FF/GB pMDI formulation, therefore supporting reformulation using a propellant with low global warming potential.

Overcoming the Low-Stability Bottleneck in the Clinical Translation of Liposomal Pressurized Metered-Dose Inhalers: A Shell Stabilization Strategy Inspired by Biomineralization.

Currently, several types of inhalable liposomes have been developed. Among them, liposomal pressurized metered-dose inhalers (pMDIs) have gained much attention due to their cost-effectiveness, patient compliance, and accurate dosages. However, the clinical application of liposomal pMDIs has been hindered by the low stability, i.e., the tendency of the aggregation of the liposome lipid bilayer in hydrophobic propellant medium and brittleness under high mechanical forces. Biomineralization is an evolutionary mechanism that organisms use to resist harsh external environments in nature, providing mechanical support and protection effects. Inspired by such a concept, this paper proposes a shell stabilization strategy (SSS) to solve the problem of the low stability of liposomal pMDIs. Depending on the shell material used, the SSS can be classified into biomineralization (biomineralized using calcium, silicon, manganese, titanium, gadolinium, etc.) biomineralization-like (composite with protein), and layer-by-layer (LbL) assembly (multiple shells structured with diverse materials). This work evaluated the potential of this strategy by reviewing studies on the formation of shells deposited on liposomes or similar structures. It also covered useful synthesis strategies and active molecules/functional groups for modification. We aimed to put forward new insights to promote the stability of liposomal pMDIs and shed some light on the clinical translation of relevant products.

Development of a self-microemulsifying drug delivery system to deliver delamanid via a pressurized metered dose inhaler for treatment of multi-drug resistant pulmonary tuberculosis.

Tuberculosis (TB) is a serious health issue that contributes to millions of deaths throughout the world and increases the threat of serious pulmonary infections in patients with respiratory illness. Delamanid is a novel drug approved in 2014 to deal with multi-drug resistant TB (MDR-TB). Despite its high efficiency in TB treatment, delamanid poses delivery challenges due to poor water solubility leading to inadequate absorption upon oral administration. This study involves the development of novel formulation-based pressurized metered dose inhalers (pMDIs) containing self-microemulsifying mixtures of delamanid for efficient delivery to the lungs. To identify the appropriate self-microemulsifying formulations, ternary diagrams were plotted using different combinations of surfactant to co-surfactant ratios (1:1, 2:1, and 3:1). The combinations used Cremophor RH40, Poly Ethylene Glycol 400 (PEG 400), and peppermint oil, and those that showed the maximum microemulsion region and rapid and stable emulsification were selected for further characterization. The diluted self-microemulsifying mixtures underwent evaluation of dose uniformity, droplet size, zeta potential, and transmission electron microscopy. The selected formulations exhibited uniform delivery of the dose throughout the canister life, along with droplet sizes and zeta potentials that ranged from 24.74 to 88.99 nm and - 19.27 to - 10.00 mV, respectively. The aerosol performance of each self-microemulsifying drug delivery system (SMEDDS)-pMDI was assessed using the Next Generation Impactor, which indicated their capability to deliver the drug to the deeper areas of the lungs. In vitro cytotoxicity testing on A549 and NCI-H358 cells revealed no significant signs of toxicity up to a concentration of 1.56 µg/mL. The antimycobacterial activity of the formulations was evaluated against Mycobacterium bovis using flow cytometry analysis, which showed complete inhibition by day 5 with a minimum bactericidal concentration of 0.313 µg/mL. Moreover, the cellular uptake studies showed efficient delivery of the formulations inside macrophage cells, which indicated the potential for intracellular antimycobacterial activity. These findings demonstrated the potential of the Delamanid-SMEDDS-pMDI for efficient pulmonary delivery of delamanid to improve its effectiveness in the treatment of multi-drug resistant pulmonary TB.

Medicaciones inhaladas y cámaras de inhalación para el asma infantil. Red española de grupos de trabajo sobre asma en pediatría (REGAP) / Inhaled medications and inhalation chambers for childhood asthma. Spanish network of working groups on asthma in pediatrics (REGAP)

El asma, la enfermedad crónica más prevalente en la edad pediátrica, continúa planteando desafíos en su manejo y tratamiento1. Guías nacionales e internacionales destacan la importancia de la educación terapéutica (ET) para lograr el control de esta enfermedad2,3. Esta educación implica la transmisión de conocimientos y habilidades al paciente y su familia, mejorando la adherencia a la medicación, corrigiendo errores en la técnica de inhalación y ajustando el tratamiento según las características individuales de cada paciente4,5. Es esencial que la ET sea progresiva, gradual e individualizada, y que esté presente en todos los niveles asistenciales. La formación en ET de profesionales sanitarios es crucial, especialmente para los pediatras, quienes además deben conocer la extensa variabilidad de medicamentos e inhaladores disponibles y sus indicaciones para cada edad6. Para abordar esta necesidad, el Grupo red española de grupos de trabajo sobre asma en pediatría (REGAP) ha revisado exhaustivamente los inhaladores actualmente disponibles en España para el tratamiento del asma en la edad pediátrica. La revisión incluye una revisión de los distintos sistemas de inhalación y los distintos fármacos inhalados, utilizados para el tratamiento del asma en la edad pediátrica. Esta revisión se actualizará anualmente, incluyendo información sobre fármacos, dispositivos, cámaras de inhalación, indicaciones y financiación. El Grupo REGAP espera que estas tablas sean una valiosa ayuda para los pediatras en su práctica clínica diaria y constituyen una eficaz herramienta de ET.(AU)

Asthma, the most prevalent chronic disease in pediatric age, continues to pose challenges in its management and treatment. National and international guidelines emphasize the importance of therapeutic education (TE) to achieve disease control. TE involves imparting knowledge and skills to the patient and their family, enhancing medication adherence, rectifying errors in inhalation technique, and tailoring treatment based on individual patient characteristics. It is essential for TE to be progressive, gradual, and personalized, spanning all levels of care. Training healthcare professionals in TE is crucial, particularly for pediatricians, who must also be aware of the extensive variability of available meds and inhalers and their respective age-specific indications. Addressing this need, the REGAP Group extensively reviewed inhalers currently available in Spain for pediatric asthma treatment. The review encompassed different inhalation systems and inhaled drugs used for pediatric asthma treatment. This review will be updated annually, providing information on medications, devices, inhalation chambers, indications, and financiation. The REGAP Group hopes that these tables will be a valuable help for pediatricians in their daily clinical practice and serve as an effective TE tool.(AU)

Demystifying Dry Powder Inhaler Resistance with Relevance to Optimal Patient Care.

The selection of an inhaler device is a key component of respiratory disease management. However, there is a lack of clarity surrounding inhaler resistance and how it impacts inhaler selection. The most common inhaler types are dry powder inhalers (DPIs) that have internal resistance and pressurised metered dose inhalers (pMDIs) that use propellants to deliver the drug dose to the airways. Inhaler resistance varies across the DPIs available on the market, depending largely on the design geometry of the device but also partially on formulation parameters. Factors influencing inhaler choice include measures such as flow rate or pressure drop as well as inhaler technique and patient preference, both of which can lead to improved adherence and outcomes. For optimal disease outcomes, device selection should be individualised, inhaler technique optimised and patient preference considered. By addressing the common clinically relevant questions, this paper aims to demystify how DPI resistance should guide the selection of the right device for the right patient.

Selection of the right inhaler is important to ensure that patients with respiratory diseases get the most benefit from their treatment. Dry powder inhalers and pressurised metered dose inhalers are the most common inhaler types. Pressurised metered dose inhalers use propellants to deliver the drug to the lungs. In contrast, dry powder inhalers deliver the drug to the lungs by having internal resistance. This restricts the flow of air through the inhaler. As the patient inhales through the inhaler, the resistance against the air flow generates the power to separate the drug molecules and carry them to the lungs. While there are many factors to be considered for inhaler selection, there is often confusion around how resistance should guide selection of inhaler. With low-resistance devices, patients must inhale faster to generate the power to separate the drug molecules, which may be difficult in patients with poor lung function. With high-resistance devices, patients do not need to inhale as fast to separate the drug, and most patients can effectively use the inhaler. This article addresses the common clinically relevant questions to clarify how the internal resistance of the inhaler should be used to help guide the selection of the right device for the right patient.

Enhancing Inhalation Drug Delivery: A Comparative Study and Design Optimization of a Novel Valved Holding Chamber.

This paper presents an innovative approach to the design optimization of valved holding chambers (VHCs), crucial devices for aerosol drug delivery. We present the design of an optimal cylindrical VHC body and introduce a novel valve based on particle impaction theory. The research combines computational simulations and physical experiments to assess the performance of various VHCs, with a special focus on the deposition patterns of medication particles within these devices. The methodology incorporates both experimental and simulation approaches to validate the reliability of the simulation. Emphasis is placed on the deposition patterns observed on the VHC walls and the classification of fine and large particles for salbutamol sulfate particles. The study reveals the superior efficacy of our valve design in separating particles compared to commercially available VHCs. In standard conditions, our valve design allows over 95% of particles under 7 µm to pass through while effectively filtering those larger than 8 µm. The optimized body design accomplishes a 60% particle mass flow fraction at the outlet and an average particle size reduction of 58.5%. When compared numerically in terms of size reduction, the optimal design outperforms the two commercially available VHCs selected. This study provides valuable insights into the optimization of VHC design, offering significant potential for improved aerosol drug delivery. Our findings demonstrate a new path forward for future studies, aiming to further optimize the design and performance of VHCs for enhanced pulmonary drug delivery.

Promoting knowledge of metered dose inhaler (MDI) usage among pharmacy professional students through a mobile app.

INTRODUCTION: Efficient asthma management necessitates optimal usage of metered-dose inhalers (MDIs). As future health professionals, pharmacy students are pivotal in disseminating accurate methodologies for MDI usage. Despite having hands-on experience, there is room to enhance their comprehension, highlighting the need for prompt patient educational interventions. OBJECTIVE: This study aims to evaluate the effectiveness of a mobile app-assisted educational method in improving pharmacy students' understanding of MDI usage. METHODS: A pre-experimental study was conducted from March to August 2021 with 45 participants enrolled in the Pharmacist Professional Study Program at the Faculty of Medicine and Health Sciences, Universitas Muhammadiyah Yogyakarta. Using a one-group pretest-post-test design, the study measured the app's impact on students' knowledge and MDI usage skills. RESULTS: The intervention significantly improved students' scores on a 9-step MDI usage checklist, with increases ranging from 0.10 to 0.50 across verbal and motor components. A Mann-Whitney U test validated these findings, showing a statistically significant p-value of 0.001. CONCLUSION: The mobile app-assisted educational approach substantially enhanced pharmacy students' proficiency in MDI use. The significant rise in mean scores for the 9-step checklist, along with the notable p-value, supports the effectiveness of this intervention in healthcare education.

Simultaneous UPLC Assay for Oxitropium Bromide and Formoterol Fumarate Dihydrate in Pressurized Metered Dose Inhaler Products for Chronic Obstructive Pulmonary Disease.

BACKROUND: Oxitropium bromide (OB) and formoterol fumarate dihydrate (FFD) are inhaler molecules that are widely used in the treatment of chronic lung diseases. OBJECTIVE: The goal of this work was to create a reversed phase-ultra performance liquid chromatography (RP-UPLC) technique for assay and identification of OB and FFD, as well as identification and estimate of its associated compounds in pressurized metered dose inhaler product (pMDI). METHOD: Separation of oxitropium and formoterol peaks were enhanced on a C18 (50 × 2.1 mm × 1.7 µm) UPLC column with ethylene-bridged-hybrid technology, The mobile phase consists of buffer (0.07 M KH2PO4) and acetonitrile (80:20, v/v). The detector wavelength of 210 nm, flow rate of pump 0.6 mL/min, and oven temperature for column were set at 25°C. The injection volume was 10 µL. The method run time was 2 min. The mobile phase was used as the solvent. RESULTS: Retention times (RTs) were 0.5 min for OB and 1.0 min for FFD. The assay analysis was linear range for all analytes within the range for concentrations 0.03-14.8 µg/mL of OB, 0.01-0.88 µg/mL of FFD. LOD values and LOQ values 0.009 and 0.026 µg/mL for OB and 0.003 and 0.009 µg/mL for FFD, respectively. Recoveries were obtained at 96.3% for OB and 97.2% for FFD. Precisions values were (as RSD, %) ≤1.5%. CONCLUSIONS: With the UPLC method developed and validated according to the current ICH guidelines, it is possible to simultaneously detect OB and FFD of assay analysis in pMDI products accurately, precisely and selectively, independent of the matrix effect. HIGHLIGHTS: The present method is the first method in the literature based on the UPLC method for this purpose. The UPLC method is a time-saving method, it provides a faster and cheaper technique than the high performance liquid chromatography (HPLC) method.

Application of different counseling strategies for better adult asthma control.

OBJECTIVE: We aimed to compare the effectiveness of three distinct counseling methods to determine the most effective approach. METHODS: In this prospective cohort study with a two-month follow-up, A group of non-smoking adults, aged 19-60 years, were randomly collected at outpatients clinic with prior asthma diagnosis, based on the forced expiratory volume in one seconds to forced vital capacity ratio (FEV1/FVC) and the guidelines outlined by the Global Initiative for Asthma (GINA), At the baseline assessment, all patients, underwent FEV1/FVC measurements, asthma symptom evaluations using Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), and GINA symptoms control assessment questionnaire, and assessment of pressurized metered-dose inhaler (pMDI) usage. The patients were divided into three groups, each assigned a distinct counseling strategy: traditional verbal counseling, advanced counseling utilizing the Asthma smartphone-application, and a combination of advanced-verbal counseling. We conducted a two-month monitoring period for all three groups. RESULTS: Significant differences (p < .001) were observed among the three counseling groups in ACT, FEV1/FVC ratio, and GINA symptoms control assessment scores from the first month to the second month visit. Regarding ACQ, the study unveiled a noteworthy disparity in ACQ scores during the second week, with a significant difference (p = .025) observed between the verbal and advanced-verbal counseling groups. Similarly, a significant difference (p = .016) was noted between the advanced counseling group and the advanced-verbal counseling groups. CONCLUSION: The study findings indicate that the combining advanced-verbal counseling by incorporating the Asthma smartphone-application alongside traditional verbal counseling is a more effective approach for improving asthma control in adults.

Does mixing inhaler devices lead to unchecked inhaler technique errors in patients with COPD? Findings from the cross-sectional observational MISMATCH study.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) may be prescribed multiple inhalers that require different techniques for optimal performance. Mixing devices has been associated with poorer COPD outcomes suggesting that it leads to inappropriate inhaler technique. However, empirical evidence is lacking. AIMS: Compare the nature and frequency of dry powder inhaler (DPI) technique errors in patients with COPD using (1) a single DPI or (2) mixed-devices (a DPI and pressurised metered dose inhaler (pMDI)). METHODS: Data from the PIFotal study-a cross-sectional study on Peak Inspiratory Flow in patients with COPD using a DPI as maintenance therapy, capturing data from 1434 patients on demographic characteristics, COPD health status and inhaler technique-were used to select 291 patients using mixed-devices. Frequency matching based on country of residence and DPI device type was used to select 291 patients using a DPI-only for comparison. Predetermined checklists were used for the evaluation of DPI video recordings and complemented with additional errors that were observed in ≥10%. Error proportions were calculated for the (1) individual and total number of errors, (2) number of critical errors and (3) number of pMDI-related errors. RESULTS: The study sample contained 582 patients (mean (SD) age 69.6 (9.4) years, 47.1% female). DPI technique errors were common, but not significantly different between the groups. The majority of patients made at least one critical error (DPI-only: 90.7% vs mixed-devices: 92.8%). Proportions of total, 'pMDI-related' and critical errors did not significantly differ between the groups. CONCLUSION: The nature and frequency of inhaler technique errors did not substantially differ between patients prescribed with a single DPI and mixed-devices. Currently, 'pMDI-related errors' in DPI use are not accounted for in existing checklists. TRIAL REGISTRATION NUMBER: ENCEPP/EUPAS48776.

Evaluación e impacto de la educación de la técnica inhalatoria en pacientes adultos que usan inhalador de dosis medida / Evaluation and Impact of Education on the Inhalation Technique in Adults who Use a Metered Dose Inhaler

Introducción: los inhaladores de dosis medida (MDI) ocupan un lugar fundamental en el tratamiento de las enfermedades obstructivas. Sin embargo, existe evidencia de su in-correcta utilización y, por consiguiente, limitados beneficios. El objetivo de este traba-jo es evaluar el uso de los MDI y conocer el impacto que tiene la educación en la técnica inhalatoria. Método: estudio prospectivo, antes-después realizado en pacientes hos-pitalizados y ambulatorios. Se registraron datos demográficos y sobre el uso del MDI. Posteriormente, se pidió al paciente que realizara dos inhalaciones con su MDI y aero-cámara, se otorgó un puntaje según la escala ESTI y se educó en forma oral, visual y con folleto explicativo. Los pacientes fueron reevaluados antes de cumplir un mes de la primera evaluación. Resultados: se incluyeron 119 pacientes, 53,8% masculinos, con edad media de 60,6 (± 16) años. El 60,5% utilizaba aerocámara siempre y el 19,3% casi siempre. El 65% tenía la percepción de que su técnica inhalatoria era buena o muy bue-na. El 32% no sabía identificar su inhalador de rescate. El puntaje en la escala ESTI ba-sal fue de 6,8 (± 2,3) ptos. el que mejoró en la reevaluación, 8,7 (± 1,5) ptos.; p<0,0001. La técnica inhalatoria calificada de muy buena o buena mejoró de un 24,4% a un 63%; p<0.0001. Conclusión: nuestros resultados muestran que la técnica de inhalación con MDI es deficiente y una educación activa evidencia un impacto significativo en el co-rrecto uso de estos dispositivos. (AU)

Introduction: metered dose inhalers (MDI) are fundamental in treating obstructive dis-eases. However, there is evidence of its incorrect use and therefore limited benefits. This work aims to evaluate the use of MDIs and to know the impact of education on the cor-rect inhalation technique. Method: prospective, before-after study, carried out in hospitalized and outpatients. Demographic data and data on the use of the MDI are re-corded. Subsequently, the patient was asked to take 2 inhalations with his MDI and valved-holding chamber, a score was given according to the ESTI score and he was ed-ucated orally, visually, and with an explanatory brochure. The patients were reassessed within 1 month of the first evaluation. Results: 119 patients were included, 53.8% male, with a mean age of 60.6 (±16) years. 60.5% always used an aero chamber and 19.3% almost always. 65% had the perception that their inhalation technique was good or very good. 32% did not know how to identify their rescue inhaler. The score on the base-line ESTI scale was 6.8 (± 2.3) points, which improved in the reassessment, 8.7 (± 1.5) points; p<0.0001. The inhalation technique rated as very good or good improved from 24.4% to 63%; p<0.0001. Conclusion: our results show that the inhalation technique with MDI is deficient and active education demonstrates a significant impact on the cor-rect use of these devices. (AU)