Formoterol Research Articles

Comparison of extrafine beclomethasone dipropionate/formoterol fumarate dry powder inhaler and pressurized metered-dose inhaler in Chinese patients with asthma: the FORTUNE study

Objective When selecting inhaled therapies, it is important to consider both the active molecules and the device. Extrafine formulation beclomethasone dipropionate plus formoterol fumarate (BDP/FF) has been available for some years delivered via pressurized metered-dose inhaler (pMDI). More recently, a breath-activated, multi-dose dry-powder inhaler (DPI), the NEXThaler, has been approved. The current study aimed to demonstrate the non-inferiority of BDP/FF delivered via the DPI vs. via the pMDI, in Chinese adults with asthma. Methods After a four-week run-in period, when all patients received BDP/FF pMDI 100/6 µg, two inhalations twice daily (BID), patients were randomized equally to BDP/FF pMDI or DPI, both 100/6 µg, two inhalations BID for 12 weeks. The primary objective was to demonstrate non-inferiority of BDP/FF DPI vs. BDP/FF pMDI in terms of average pre-dose morning peak expiratory flow (PEF) over the entire treatment period. Results Of 252 and 242 patients in the DPI and pMDI groups, respectively, 88.5% and 88.8% completed the study. The primary objective was met, with no statistically significant difference between the treatments in average pre-dose morning PEF, and with the lower limit of the 95% CI above the −15 L/min non-inferiority margin (adjusted mean difference: 5.25 L/min [95% CI: −0.56, 11.06]). Adverse events were reported by 48.4% and 49.6% patients in the DPI and pMDI groups, respectively, most mild or moderate. Conclusions The NEXThaler DPI is a similarly effective device to the pMDI for the administration of BDP/FF in adults, so extending the options available for the management of asthma.

Effectiveness of combined use of formoterol fumarate tablets and interventional bronchoscopy in the treatment of central airway tumor

Purpose: To study the effectiveness of formoterol fumarate tablets when used in combination with interventional bronchoscopy for central airway tumor.Methods: A total of 154 central airway tumor patients on admission in Second Affiliated Hospital of Zunyi Medical University, Zunyi, China (August 2020 - December 2022) were assigned to benign group (BG, n = 70) and malignant group (MG, n = 84), based on the nature of tumor lesion. The patients were administered formoterol fumarate tablets as well as interventional bronchoscopy. Clinical efficacy, lung function indices such as forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio, blood gas indices (pH, partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2)), scores on shortness of breath, and survival rate, were determined and compared between the two groups.Results: The overall effectiveness in BG (97.14 %) was significantly higher than that in MG (84.52 %). There were higher post-treatment values of FEV1, FVC and FEV1/FVC; higher values of pH and PaO2, lower PaCO2, and lower scores on shortness of breath in BG and MG, relative to pre- treatment levels (p < 0.05). Follow-up showed no recurrence in patients with benign tumor, and clinical efficacy was satisfactory. The 2-year survival rate of patients with malignant tumor was 51.19 %.Conclusion: The combination of formoterol fumarate tablets and interventional bronchoscopy produces significant curative effect on benign and malignant tumor in central airway. It improves lung function, blood gas indices and survival rate, and mitigates shortness of breath. Therefore, this treatment strategy has a high potential for use in clinical practice.

Small airway disease in post-acute COVID-19 syndrome, a non-conventional approach in three years follow-up of a patient with long COVID: a case report

BackgroundSmall airways disease (SAD), a novel finding described in post-acute COVID-19 patients, should be suspected when respiratory symptoms continue, air trapping persists on expiratory CT scans, and imaging findings fail to improve despite objectively better conventional pulmonary function test (PFT) parameters. The forced oscillation technique (FOT) and Multiple breathing washout (MBW) are both very sensitive methods for detecting anomalies in the peripheral airways.Case presentationWe discuss the case of a 60-year-old Hispanic patient who had severe COVID-19 pneumonia and developed dyspnea, fatigue, and limited daily activity a year later. The PFTs revealed restrictive lung disease, as seen by significant diffusing capacity of the lungs for carbon monoxide (DLCO) decrease, severe desaturation, and poor 6-min walk test (6MWT) performance. The patient was treated with lowering corticosteroids as well as pulmonary rehabilitation (PR). During the 24-month follow-up, the dyspnea and fatigue persisted. On PFTs, 6MWT performance and restricted pattern improved slightly, but MBW discovered significant ventilatory inhomogeneity. FOT revealed substantial peripheral airway obstructive abnormalities. On CT scans, air trapping and ground-glass opacities (GGO) improved somewhat. The patient used a bronchodilator twice a day and low-dose inhaled corticosteroids (160 µg of budesonide and 4.5 µg of formoterol fumarate dihydrate) for nine months. PR sessions were resuming. The restricting parameters were stabilized and the DLCO had normalized after 36 months, with a 6MWT performance of 87% but significant desaturation. The CT scan revealed traction bronchiectasis, low GGO, and persistent air trapping. Without normalization, FOT and MBW scores improved, indicating small airway disease.ConclusionsThe necessity of integrating these tests when detecting SAD is emphasized in our paper. This article lays the foundation for future research into the best ways to manage and monitor SAD in post-acute COVID-19 patients.

Acute Effects of Single Versus Combined Inhaled β2-Agonists Salbutamol and Formoterol on Time Trial Performance, Lung Function, Metabolic and Endocrine Variables

BackgroundHigh prevalence rates of β2-agonist use among athletes in competitive sports makes it tempting to speculate that illegitimate use of β2-agonists boosts performance. However, data regarding the potential performance-enhancing effects of inhaled β2-agonists and its underlying molecular basis are scarce.MethodsIn total, 24 competitive endurance athletes (12f/12m) participated in a clinical double-blinded balanced four-way block cross-over trial to investigate single versus combined effects of β2-agonists salbutamol (SAL) and formoterol (FOR), to evaluate the potential performance enhancement of SAL (1200 µg, Cyclocaps, Pb Pharma GmbH), FOR (36 µg, Sandoz, HEXAL AG) and SAL + FOR (1200 µg + 36 µg) compared to placebo (PLA, Gelatine capsules containing lactose monohydrate, Pharmacy of the University Hospital Ulm). Measurements included skeletal muscle gene and protein expression, endocrine regulation, urinary/serum β2-agonist concentrations, cardiac markers, cardiopulmonary and lung function testing and the 10-min time trial (TT) performance on a bicycle ergometer as outcome variables. Blood and urine samples were collected pre-, post-, 3 h post- and 24 h post-TT.ResultsMean power output during TT was not different between study arms. Treatment effects regarding lung function (p < 0.001), echocardiographic (left ventricular end-systolic volume p = 0.037; endocardial global longitudinal strain p < 0.001) and metabolic variables (e.g. NR4A2 and ATF3 pathway) were observed without any influence on performance. In female athletes, total serum β2-agonist concentrations for SAL and FOR were higher. Microarray muscle gene analysis showed a treatment effect for target genes in energy metabolism with strongest effect by SAL + FOR (NR4A2; p = 0.001). Of endocrine variables, follicle-stimulating hormone (3 h Post–Post-TT), luteinizing hormone (3 h Post–Pre-TT) and insulin (Post–Pre-TT) concentrations showed a treatment effect (all p < 0.05).ConclusionsNo endurance performance-enhancing effect for SAL, FOR or SAL + FOR within the permitted dosages compared to PLA was found despite an acute effect on lung and cardiac function as well as endocrine and metabolic variables in healthy participants. The impact of combined β2-agonists on performance and sex-specific thresholds on the molecular and cardiac level and their potential long-term performance enhancing or health effects have still to be determined.Trial registration: Registered at Eudra CT with the number: 2015-005598-19 (09.12.2015) and DRKS with number DRKS00010574 (16.11.2021, retrospectively registered).

The Effect of Usage of Antiasthmatic Inhalers on Color Stability and Surface Roughness of Dental Restorative Materials: An In Vitro Study.

Increased demand for esthetics by parents and children has resulted in the use of tooth-colored restorative materials. Children with chronic respiratory conditions like asthma use inhalers which have shown to affect the surface of restorative materials. Hence, the aim of the present study was to evaluate the effect of antiasthmatic inhalers on color stability and surface roughness of three restorative materials. Forty samples each of three dental restorative materials: group A: glass ionomer cement (GIC), group B: alkasite restorative material, and group C: composite resins were prepared. Each group was further divided into two subgroups of 20 samples each according to the inhaler used. All the specimens were polished using polishing discs and stored in artificial saliva in order to simulate the oral environment. The baseline color value and surface roughness of all the samples were measured using a spectrophotometer and a profilometer, respectively. Group 1 and group 2 were exposed to 0.31 mg of salbutamol sulfate and 20 mg formoterol fumarate in combination with budesonide, respectively, for every 12 hours, for a period of 15 days following which the samples were evaluated for color changes and surface roughness. The data obtained was subjected to statistical analysis and level of significance was set at p < 0.05. Exposure to both the inhalers caused a change in color and surface roughness in all three restorative materials. There was a significant change in the color of GIC and composite resin (ΔE > 3.3), following exposure to both the inhalers (p < 0.05). The change in color of alkasite restorative material was not significant. A significant increase in the surface roughness of composite resin from 0.56 ± 0.14 to 0.67 ± 0.19 was seen following 15 days' exposure to formoterol in combination with budesonide inhaler (p < 0.05). Following exposure, both the inhalers had an equal effect on color and surface roughness of all three restorative materials. Alkasite restorative material showed greater resistance to change in color and surface roughness when exposed to antiasthmatic inhalers, compared to GIC and composite resin. Thus, children who use inhalers and nebulizers should be advised to implement more precautionary oral hygiene measures and periodic dental visits.

Evolving to a single inhaler extrafine LABA/LAMA/ICS – Inhalation technique and adherence at the heart of COPD patient care (TRIVOLVE)

ObjectiveIncorrect inhaler use and poor treatment adherence have a negative impact on COPD outcomes. This multi-centre, single arm, non-interventional, phase IV study investigated whether inhalation technique, treatment adherence and patient outcomes change in patients who evolve from dual therapy or multiple inhaler triple therapy to single inhaler extrafine triple therapy (beclomethasone dipropionate (BDP, 87 μg), formoterol fumarate (FF, 5 μg) and glycopyrronium (G, 9 μg)) in combination with inhalation technique training. MethodsA total of 126 COPD patients were included in the per protocol set. Inhalation technique and treatment adherence were assessed at baseline and at two visits at approximately 3 and 6 months of treatment with extrafine BDP/FF/G. In addition, lung function, symptom score, patient satisfaction and exacerbations (exploratory) were followed up. ResultsBefore switching to single inhaler extrafine BDP/FF/G (baseline), any device errors and critical errors were detected for 28.8% and 9.6% of patients, respectively. After switching to BDP/FF/G, the percentage of patients with any device errors decreased to 14.0% (visit 2) and 16.3% (visit 3), without critical errors at the two follow-up visits. Treatment adherence increased from 67.5% at baseline to 75.8% (visit 2) and 80% (visit 3). In addition, lung function, symptom and patient satisfaction scores improved, whilst exacerbation rates substantially decreased. ConclusionsThis observational study demonstrates that in eligible COPD patients in a real-life setting, the switch from dual therapy or multiple inhaler triple therapy to single inhaler extrafine BDP/FF/G in combination with inhalation technique training is associated with improved inhalation technique and adherence.

Airway smooth muscle area to predict steroid responsiveness in COPD patients receiving triple therapy (HISTORIC): a randomised, placebo-controlled, double-blind, investigator-initiated trial.

Although inhaled corticosteroids (ICS) are highly effective in asthma, they provide significant but modest clinical benefit in COPD. Here, we tested the hypothesis that high bronchial airway smooth muscle (ASMC) area in COPD is associated to ICS responsiveness.In this investigator-initiated and -driven, double-blind, randomised, placebo-controlled trial (HISTORIC), 190 COPD patients, GOLD stage B-D, underwent bronchoscopy with endobronchial biopsy. Patients divided in groups A and B with high ASMC area (HASMC: >20% of the bronchial tissue area) and with low ASMC area (LASMC: ≤20% of the bronchial tissue area), respectively and followed a run-in period of 6 weeks on open-label triple inhaled therapy with aclidinium/formoterol/budesonide (ACL/FOR/BUD:400/12/400 mcg/bid). Subsequently, patients were randomised to receive either ACL/FOR/BUD or ACL/FOR/Placebo and followed for 12 months. The primary end point of the study was the difference in post-bronchodilator FEV1 over 12 months between patients with LASMC and HASMC receiving or not receiving ICS.In patients with LASMC, ACL/FOR/BUD did not significantly improve FEV1 over 12 months, as compared to ACL/FOR/placebo p=0.675. In patients with HASMC, however, ACL/FOR/BUD significantly improved FEV1, as compared to ACL/FOR/placebo p=0.020. Over 12 months, the difference of FEV1 change between the group of ACL/FOR/BUD and the group of ACL/FOR/placebo was 50.6 mL·year-1 within the group of patients with LASMC and 183.0 mL·year-1 within the group of patients with HASMC.COPD patients with ΗASMC respond better to ICS than patients with LASMC, suggesting that this type of histological analysis may predict ICS responsiveness in COPD patients receiving triple therapy.

The role of capsule aperture size on the dispersion of carrier-based formulation at different air flowrates

The effect of capsule aperture size on the aerosol performance of lactose blend formulation was studied using Foradil® (containing 12 μg of formoterol fumarate (FF11A list of all acronyms used in this paper can be found in the section “Abbreviations & Symbols.”.) and 24 mg of lactose) dispersed with a powder inhaler Aerolizer® at increasing air flowrates. Apertures sizes of 0.4, 1.0, 1.5, 2.5, and 4.0 mm were introduced at the opposite ends of the capsule. The formulation was dispersed into a Next Generation Impactor (NGI) at 30, 60 and 90 L/min, with the fine particle fractions (FPFrec and FPFem) measured by chemical assay of FF and lactose using high-performance liquid chromatography. Particle size distribution (PSD) of FF particles dispersed in wet media was also characterized by laser diffraction. FPFrec showed a stronger dependency on the flowrate than the capsule aperture size. The most efficient dispersion was achieved at 90 L/min. At a given flowrate, FPFem remained broadly constant across different aperture sizes. The laser diffraction studies demonstrated the presence of large agglomerates.

Combinatory in vitro effects of the β2-agonists salbutamol and formoterol in skeletal muscle cells

β2-agonists are used for the treatment of bronchoconstriction, but also abused in doping. Beside an ergogenic activity β2-agonists may have also anabolic activity. Therefore, we investigated the anabolic activity and associated molecular mechanisms of Salbutamol (SAL) and Formoterol (FOR) alone, as well as in combination in C2C12 myotubes. In differentiated C2C12 cells, dose-dependent effects of SAL and FOR (alone/in combination) on myotube diameter, myosin heavy chain (MHC) protein expression and the mRNA expression of genes involved in hypertrophy were analyzed. β2-adrenoceptor 2 (ADRB2), androgen receptor (AR) and estrogen receptor (ER) inhibitors, as well as dexamethasone (Dexa) were co-incubated with the β2-agonists and myotube diameter was determined. SAL and FOR treatment significantly induced hypertrophy and increased MHC expression and the mRNA expression of Igf1, mTOR, PIk3r1 and AMpKa2. In contrast to an ER inhibitor, the ADRB2 and AR inhibitors, as well as Dexa antagonized FOR and SAL induced hypertrophy. Combined treatment with SAL and FOR resulted in significant additive effects on myotube diameter and MHC expression. Future clinical studies are needed to prove this effect in humans and to evaluate this finding with respect to antidoping regulations.

Bronchodilator therapy in patients with chronic obstructive pulmonary disease: what should be considered in clinical practice when choosing a dosing regimen?

The use of long-acting bronchodilators is central to the chronic obstructive pulmonary disease (COPD) therapy. One of the goals of bronchodilation is to reduce the morning COPD symptoms that are associated with a more severe disease and an increased risk of exacerbations.The aim of the study was to evaluate the clinical efficacy of switching COPD patients with severe morning symptoms who received combinations of long-acting bronchodilators QD to a fixed-dose combination of aclidinium bromide (AB) and formoterol fumarate (FF) BID.Methods. We examined COPD patients treated with combinations of long-acting β2-agonists and M-anticholinergics (but not AB and FF), who continued to complain of severe symptoms in the morning despite the treatment. After examination, the patients were switched to the fixed-dose combination of AB 0.4 mg and FF 0.012 mg (AB/FF) BID in the form of a metered-dose powder inhaler. The patients were examined at baseline and at 6-month follow-up.Results. Of the 115 included COPD patients, 90 completed the study. After 6 months of treatment, they showed a significant decrease in the intensity of cough, sputum amount, severity of distant wheezing, and shortness of breath in the morning (–0.88, –0.38, –0.29, –0.58 on a 4-point scale, the mean score –0.44; p &lt; 0.001). The result of the COPD Assessment test decreased from 28 (24; 34) to 24 (20; 28) (p = 0.011), the distance of a 6-minute walk increased from 319 ± 72 to 354 ± 67 m (p &lt; 0.001). The fixed-dose combination of AB/FF did not cause serious adverse events.Conclusion. The fixed-dose AB/FF combination in COPD patients resulted in a significant clinical improvement and was well tolerated. The AB/FF combination with twice daily dosing regimen is advisable for the patients with morning symptoms persisting despite therapy with other combinations of long-acting bronchodilators with once daily dosing regimen.

Inhalable aerosol microparticles with low carrier dosage and high fine particle fraction prepared by spray-freeze-drying

Co-suspension drug-loading technology, namely Aerosphere™, can improve fine particle fraction (FPF) and delivered dose content uniformity (DDCU). However, because of its poor drug-loading efficacy, the phospholipid carrier dosage in Aerosphere™ is usually dozens of times greater than that of the drug, resulting in a high material cost and blockage of the actuator. In this study, spray-freeze-drying (SFD) technology was used to prepare inhalable distearoylphosphatidylcholine (DSPC)-based microparticles for pressurized metered-dose inhalers (pMDI). Water-soluble, low-dose formoterol fumarate was used as an indicator to evaluate the aerodynamic performance of the inhalable microparticles. Water-insoluble, high-dose mometasone furoate was used to investigate the effects of drug morphology and drug-loading mode on the drug delivery efficiency of the microparticles. The results demonstrated that DSPC-based microparticles prepared using the co-SFD technology not only achieved higher FPF and more consistent delivered dose than those of drug crystal-only pMDI, but the amount of DSPC was also reduced to approximately 4% of that prepared using the co-suspension technology. This SFD technology may also be used to improve the drug delivery efficiency of other water-insoluble and high-dose drugs.

A New Validated Method for Simultaneous Determination of Aerodynamic Particle Size Distribution of Drug Particles of Mometasone Furoate and Formoterol Fumarate Dihydrate in 200 mcg/5 mcg Inhalation Aerosol

Simultaneous determination of aerodynamic particle size distribution (APSD) of drug particles of mometasone furoate and formoterol fumarate dihydrate – 200 mcg/5 mcg inhalation aerosol (MDI) has been developed and reported in this work. The method was developed in consistent with USP &lt;601&gt; inhalation and nasal drug products e.g. aerosols, sprays and powders. The next generation impactor (NGI) was used and operated at 30 ± 5% L/min. The proposed method was demonstrated for sensitivity, minimum number of actuations, diluent volume optimization, mass balance and precision. The proposed method was found to be robust, accurate, linear and precise.

The Study of Spray-Freeze-Drying Technique for Development of Novel Combination pMDIs, Part II: In Vitro and In Vivo Evaluations

AbstractThe mometasone furoate (MF) and formoterol fumarate dihydrate (FF) inhalable microparticles prepared by different methods, such as micronized active pharmaceutical ingredients (APIs), microparticles of APIs prepared by spray-freeze drying technique (SFD APIs), and phospholipid microparticles of APIs prepared by SFD (SFD Lip-APIs), showed different inhaled drug delivery characteristics. Study on the physicochemical characteristics of those microparticles and the effect of matrix excipients on pharmacokinetic (PK) behaviors of inhalable microparticles is helpful for the development of new methods for inhalable microparticles with excellent performance of inhalation characteristics. In this study, the crystal state of the microparticles was investigated by powder X-ray diffraction and differential scanning calorimetry. The density was investigated by a bulk density method. The suspension and dispersion characteristics were determined by observing its state in hydrofluoroalkane (HFA). Meanwhile, the PK behaviors of SFD Lip-APIs in beagle dogs were also investigated by airway administration to evaluate the effect of phospholipids on drug release. The results indicated that the presence of phospholipids prevents the formation of solid bridges bonding to each other during SFD of pure drug solutions. In comparison to the conventional micronized microparticles, inhalable drug–phospholipid microparticles were easily dispersed and suspended in HFA. The embedded drugs were in a crystal state that endowed a better physical stability, and most interestingly, have similar PK behavior to the control (a mixed solution of MF/FF), suggesting that the phospholipids, as matrix excipients, had no effect on absorption. Given above, our designed SFD phospholipid microparticles may represent an efficient carrier for pulmonary delivery of MF and FF for further clinical treatment.

Cost-Effectiveness Analysis of Triple Therapy with Budesonide/ Glycopyrronium/ Formoterol Fumarate versus Dual Therapy in Patients with Chronic Obstructive Pulmonary Disease in Spain

To evaluate the cost-effectiveness of Budesonide/Glycopyrronium/Formoterol (BUD/GLY/FOR) versus LAMA/LABA and ICS/LABA, respectively, in patients with moderate to severe COPD, from the Spanish National Healthcare System (NHS) perspective. A lifetime Markov model with monthly cycle length was developed with baseline and treatment effect data from ETHOS clinical trial, together with utility values from literature and Spanish healthcare resource costs (€, 2021). A 3% annual discount rate was used for costs and benefits. The model comprised ten health states: nine forced expiratory volume in 1 second (FEV1)-related, which were divided by three levels of severity: moderate (FEV1 ≥50% and <80%); severe (FEV1 ≥30% and <50%) and very severe (FEV1 <30%) and a death state. Each FEV1-health state was divided into no exacerbation, moderate exacerbation, and severe exacerbations. An expert panel validated data and assumptions. Outcomes were measured as incremental cost per exacerbation avoided, per life year (LY) gained, and per quality-adjusted life-year (QALY) gained (ICUR). One-way (OWSA), scenario, and probabilistic sensitivity analyses (PSA) were performed. According to this cost-effectiveness analysis based on a Markov model, BUD/GLY/FOR was associated with a lower totals exacerbation per patient (12.80) compared to LAMA/LABA (13.36) and ICS/LABA (13.23) and higher LYs (10.32 vs 10.14 and 10.06, respectively) and QALYs (7.55 vs 7.41 and 7.32, respectively). The incremental costs were €850.95, and €2422.26, respectively, per exacerbation avoided, €2733.38 and €4111.15, respectively, per LY gained and €3461.19 and €4545.24 per QALY gained. OWSA showed that the model was most sensitive to the costs of treatments following discontinuation, but the ICUR remained below the cost-effectiveness threshold of €25,000 per QALY gained. In the PSA, the probability of BUD/GLY/FOR being cost-effective was 91.32% vs LAMA/LABA and 99.29% vs ICS/LABA. BUD/GLY/FOR is a cost-effective treatment strategy for Spanish NHS patients with COPD compared to dual therapies.

Assessment of extrafine beclomethasone/formoterol for the treatment of chronic obstructive pulmonary disease: A non-interventional study in a Bulgarian population

BackgroundThe beneficial effects of application of a fixed dose beclomethasone dipropionate (BDP) and formoterol fumarate (F) for the treatment of severe chronic obstructive disease (COPD) has been amply proven in well controlled clinical trials. Whether this also holds for real-world conditions and in such a heterogeneous patient population as is encountered in Bulgaria remained to be investigated. MethodsIn an observational, non-interventional study, 441 Bulgarian patients with severe COPD who were enrolled at 36 sites across the country received extrafine BDP/FF-combination therapy using the NEXThaler® DPI or the Foster® pMDI over a period of 16 weeks. At visits at the beginning, after 4 weeks and at the end of the study, alterations in lung function parameters FEV1 and FVC, disease symptoms, changes in CAT score, and patient distribution in GOLD 2017 categories A through D were assessed. ResultsA large share of the Bulgarian patients with severe COPD suffered from serious comorbidities, received additional medication, and about 2/3 were former or current smokers. Extrafine BDP/FF caused an increase in mean FEV1, FVC, a decrease of health impact as assessed by the CAT score, and a considerable shift of the share of category C and D patients towards A and B. In addition, the percentage of patients that were free of symptoms impacting everyday life such as fatigue and shortness of breath at rest increased throughout the study. A comparison of both application devices indicated that the NEXThaler® was superior in terms of lung functional aspects, as these parameters displayed a constant improvement over the observation period, whereas they plateaued at week 4 when using the pMDI. ConclusionsThe therapeutic benefits of extrafine BDP/FF known from clinical trials could also be observed in a real-world setting, even in such a heterogenous patient population as the Bulgarian. The NEXThaler® appeared to be highly efficient in this setting, opening a new choice for the lung specialist and the patient to select the one device considered most suitable and practical.

Application of Acupoint Catgut Embedding Therapy Combined with Liuzijue Breathing Exercise in the Treatment of Patients with Stable Chronic Obstructive Pulmonary Disease.

Objective To evaluate the application value of acupoint catgut embedding therapy combined with Liuzijue breathing exercise in the treatment of patients with stable chronic obstructive pulmonary disease (COPD) and its impact on immune function and quality of life. Methods A total of 100 patients with stable COPD admitted to our hospital from February 2020 to February 2021 were included and assigned to the experimental group (n = 50) and the control group (n = 50) according to the order of admission. Both groups of patients received conventional treatment. The control group was given daily inhalation of budesonide and formoterol fumarate powder for inhalation (320 ug/bottle), and the experimental group received additional acupoint catgut embedding therapy combined with Liuzijue breathing exercise. The clinical efficacy, pulmonary function indexes, activities of daily living (ADL) scores, quality of life (QOL) scores, traditional Chinese medicine (TCM) syndrome scores, the number of acute exacerbations, medical expenses, the incidence of adverse reactions, and immune indicators were compared between the two groups of patients. Results The experimental group yielded a significantly higher effective rate of treatment than the control group (P < 0.05). After the treatment, the experimental group obtained a superior outcome in terms of lung function indexes, immune function indexes, ADL and QOL scores, and the TCM syndrome scores when compared with the control group (P < 0.05). The number of acute exacerbations in the experimental group was remarkably lower than that in the control group (P < 0.05). No serious adverse reactions were observed in the two groups of patients, and no significant difference in the incidence of adverse reactions was found (P > 0.05). Conclusion Acupoint catgut embedding therapy combined with Liuzijue breathing exercise, with high safety, can improve the treatment effect and the quality of life of patients with stable COPD, which merits clinical promotion.

Flake like Copper Oxide Nanostructures and their Application in Electrocatalytic Sensing of Growth-Promoting Agents

A compact and intimate interfacial contact between the modified film and the conducting electrode is crucial for electrochemical biosensors. The direct drop-casting of nanomaterials onto the working electrode often fails to construct a compact interfacial arrangement, which results in sluggish electrode kinetics. Here, we describe a simple and cost-effective strategy to produce CuO nanostructure using a modified hydrothermal route. The in-situ growth allowed the formation of a highly ordered interconnected network of sharp flakes configured in the form of large spheres with excellent ITO surface coverage. The CuO nanostructures were highly electrochemically active toward the oxidation of β–adrenergic agonists, i.e., formoterol fumarate (FF). The analytical ability was studied by comparison of the electrochemical behavior of ITO based electrode with its glassy carbon electrode counterpart. The binder-less CuO-based ITO electrode successfully determined FF with a detection window of 0.01 µM to 0.46 µM with practical application for real broiler feed samples collected from the local poultry farms in Hyderabad, Pakistan.

DEVELOPMENT AND VALIDATION OF STABILITY INDICATING RP-HPLC METHOD FOR THE SIMULTANEOUS ESTIMATION OF ACLIDINIUM BROMIDE AND FORMOTEROL FUMARATE IN BULK AND INHALER FORMULATION

Objective: To develop a simple, accurate, precise, rapid and sensitive method for the simultaneous estimation of Formoterol fumarate and Aclidinium bromide in pharmaceutical dosage form.&#x0D; Methods: The chromatogram was run through Ascentis C18 150 x 4.6 mm, 5µ. Mobile phase containing Water: Acetonitrile taken in the ratio 60:40 was pumped through the column at a flow rate of 1.0 ml/min. The temperature was maintained at 30 °C. The optimized wavelength selected was 220 nm.&#x0D; Results: The retention times of Formoterol fumarate and Aclidinium bromide were found to be 2.953 min and 2.364 min. %RSD of the Aclidinium bromide and Formoterol fumarate was found to be 0.6 and 0.9, respectively. %Recovery was obtained as 99.81 % and 100.20% for Aclidinium bromide and Formoterol fumarate, respectively. LOD, LOQ values obtained from the Signal-to-noise ratio of Aclidinium bromide and Formoterol fumarate were 0.84 µg/ml, 2.56 µg/ml and 0.01 µg/ml, 0.03µg/ml respectively. Regression equation of Formoterol fumarate is y =9023x+268.67, and y = 4661.2x+1941.9 of Aclidinium bromide. Retention times were decreased and that run time was decreased, so the method developed was simple, rapid, sensitive and economical that can be adopted in regular quality control tests in Industries.&#x0D; Conclusion: Developed and Validated Formoterol fumarate and Aclidinium bromide in pharmaceutical dosage form by using RP-HPLC method.

The Study of Spray-Freeze-Drying Technique for Development of Novel Combination pMDIs, Part I: Study on the Preparation Method

AbstractClinically available pressurized metered-dose inhalers (pMDIs) mainly directly use micronized drugs as inhalable microparticles. Although technology for preparing pMDIs has proven to obtain clinically appropriate aerosol performance, the fine particle fraction and delivered dose content uniformity (DDCU) of pMDIs still need to be improved. DDCU problem is usually exacerbated by patients' handling errors prior to taking a dose. In this study, novel phospholipid microparticle inhalation pMDIs were prepared by a spray-freeze-drying process using mometasone furoate and formoterol fumarate dihydrate as model drugs and distearoylphosphatidylcholine as an excipient. Combined with the material composition, the atomization and freeze-drying processes were also studied. Our data showed that both atomization parameters of gas–liquid ratio and freeze-drying curve settings met the requirements of drug design. According to aerodynamic performance in vitro and DDCU evaluation, the performance of the phospholipid microparticle inhalation pMDI was better than that of the micronized drug microparticle pMDI. In conclusion, preparing pMDIs with particle engineering has the potential to ensure accuracy of quantification and to improve the efficiency of drug deposition in lungs in clinical practice.

ORAL LEUKOPLAKIA IN A SMOKING PATIENT USING INHALED FORMOTEROL AND BUDESONIDE

A 67-year-old non-White female patient was referred to our service for evaluation of a white oral lesion. The patient reported being a heavy smoker for 56 years and a 15-year history of asthma controlled with inhaled formoterol fumarate and budesonide for 15 years. Extraoral examination showed no relevant alterations. Intraoral examination revealed a nondetachable white verrucous plaque on the right side of the soft palate close to the limit with the hard palate. The lesion measured approximately 1.5 × 1.0 cm and had regular borders and well-defined limits. The differential diagnosis included oral leukoplakia and verrucous carcinoma. A biopsy was performed under local anesthesia. Histologic examination revealed epithelium with hyperkeratosis, acanthosis, and an intense inflammatory reaction in the lamina propria, suggesting oral leukoplakia. The lesion was excised and the clinical and microscopic analyses confirmed the diagnosis of oral leukoplakia. No evidence of recurrence was observed at 19-month follow-up.