Beclomethasone Research Articles

Development of a broad-spectrum one-step immunoassay for detection of glucocorticoids in milk using magnetosome-based immunomagnetic beads

Immunomagnetic beads provide novel tools for high-throughput immunoassay techniques. In this study, protein G (PG) was immobilized onto bacterial magentic particles (BMPs) using an additional cysteine residue at the C-terminus. A broad-spectrum monoclonal antibody against glucocorticoids (GCs) was attached to BMPs through PG-Fc interaction, generating BMP-PG-mIgG immunomagentic beads. A sensitive one-step immunoassay was developed for GCs based on combination of BMP-PG-mIgG and dexamethasone-horseradish peroxidase tracer (DMS-HRP). The developed assay exhibited half inhibitory concentrations (IC50) for dexamethasone (DMS), betamethasone (BMS), prednisolone (PNS), hydrocortisone (HCS), beclomethasone (BCMS), cortisone (CS), 6-α-methylprednisone (6-α-MPNS), fludrocortisone acetate (HFCS) of 0.98, 1.49, 2.42, 9.29, 1.63, 6.13, 7.3, and 4.89 ng/mL, respectively. The method showed recoveries ranging rates from 86.5 % to 117 % with a coefficient of variation less than 12.3 % in milk sample, which showed a good correlation with LC-MS/MS. Thus, the proposed assay offers a rapid and broad-spectrum screening tool for simultaneous detection of GCs in milk.

DEVELOPMENT AND VALIDATION OF NOVEL RP-HPLC METHOD FOR THE SIMULTANEOUS ESTIMATION OF SALICYLIC ACID AND BECLOMETHASONE DIPROPIONATE IN A TOPICAL OINTMENT DOSAGE FORM

Objective: The objective of the study is to develop and validate an analytical method to simultaneously estimate salicylic acid (SA) and beclomethasone dipropionate (BD) in a topical ointment formulation. Methods: The simultaneous estimation of SA and BD in a topical ointment formulation was carried out by developing and validating a novel, accurate, and economical isocratic reversed-phase high-performance liquid chromatographic (RP-HPLC) method. Separation was achieved by chromatographic technique using a prontosil HPLC C18 (250×4.6 mm) column with a particle size of 5 μm. The mobile phase utilized for this study includes methanol, acetonitrile, and 0.1% orthophosphoric acid in the ratio 50:35:15 v/v/v, respectively. The flow rate of 1 mL/min and column temperature of 28±2°C were set. The detection of the two drugs was carried out at 235 nm using an ultraviolet detector. It was observed that SA and BD were retained at 3.59 min and 6.00 min, respectively. Results: The RP-HPLC method was found to be linear with excellent correlation between peak areas and concentrations of 30–108 µg/mL for SA and 1–3.6 µg/mL for BD. The observed recovery data was obtained within the acceptance range of 98–102%, which confirmed the accuracy of the developed method. The two drugs, SA and BD, showed good resolution with a short analysis time of 7 min. Conclusion: The method was successfully created and validated in compliance with the recommendations of the International Conference on Harmonization for specificity, precision, linearity, accuracy, and robustness.

Characterization of isolated and integrated clinical and dermoscopic features of topical steroid-dependent/damaged face: A study from central India

ABSTRACT Background: Topical steroid-dependent/damaged face (TSDF) is defined as semi-permanent or permanent damage to the skin of the face due to unsupervised or prolonged application of topical corticosteroids to the face. Dermoscopy is widely practiced as a non-invasive, effective technique to analyze the immediate or delayed features of TSDF. Objectives: The objective was to evaluate the clinical profile along with dermoscopic features of clinically diagnosed cases of TSDF. Materials and Methods: The study was conducted on seventy-five patients attending the Department of Dermatology, Venereology, and Leprosy between April 2021 and September 2022 with clinical symptoms and signs suggestive of TSDF. Thorough history taking, clinical evaluation, and dermoscopic examination were performed, and data was recorded in a structured proforma with a sixteen-point questionnaire. Results: Sixty-eight percent of the patients were females, yielding a female-to-male ratio of 2.1:1. The most frequently affected age group was 26–35 years (48%), with a mean age of 31.8 years. The most common topical steroid employed was beclomethasone dipropionate 0.25% (33.33%), followed by clobetasol propionate 0.05% (29.33%). The most common clinical findings observed were erythema with hyperpigmentation (74.66%), followed by erythema with telangiectasia (34.66%). The most often observed dermoscopic findings were red, diffuse areas with vessels (61.33%), red, diffuse areas with an exaggerated pigment network (52%), and clustered vellus hairs with white vellus hair (44%). Conclusion: Topical corticosteroids are commonly abused drugs seen in modern clinical practice, resulting in a plethora of symptoms and creating a paramount dermatological concern. Dermoscopy plays a cardinal evaluating role in the early discernment and establishment of TSDF besides determining the gravity of damage. Key words: Topical steroid-dependent/damaged face (TSDF), Topical corticosteroids, Dermoscopy

ФІКСОВАНА КОМБІНАЦІЯ ЕКСТРАМІЛКОДИСПЕРСНОГО БЕКЛОМЕТАЗОНУ ДИПРОПІОНАТУ ТА ФОРМОТЕРОЛУ — НОВІ МОЖЛИВОСТІ В ПОКРАЩЕННІ КОНТРОЛЮ АСТМИ

Despite the great work done in recent years on the dissemination and implementation of asthma recommendations, the level of control of the disease in the world and in Europe remains unsatisfactory in a significant percentage of patients. Factors associated with the treatment failure in patients with obstructive lung diseases are not only the low adherence to the prescribed drug therapy, incorrect use of the device (poor inhalation technique), insufficient communication between the physician and the patient, inadequate drug treatment. There are other factors associated with the disease: asthma and COPD are inflammatory disorders of the entire bronchial tree, including the peripheral airways. Their involvement may remain functionally and clinically silent until signs of air trapping and hyperinflation become apparent, resulting in a lack of symptom control despite conventional treatment. Inflammatory and functional changes in the small airways (<2 mm in diameter) contribute significantly to the pathogenesis of asthma in terms of bronchoconstriction and hyperreactivity. Today, the awareness of their role in the development of asthma is increasing and they are considered as a potential target for therapy aimed at achieving and maintaining optimal disease control. The determination of the role of the distal parts of the respiratory tract predicted the need for the development of a new generation inhalers that could generate aerosols with extra-fine particles of drugs for more effective penetration of the aerosol to the periphery of the lungs. The recent appearance of inhaled extra-fine particles inhaled drugs allows for a more uniform distribution of the active substance throughout the respiratory tract, including the peripheral airways. These drugs are more effective and require a lower nominal dose to achieve the same effect on lung function and symptoms compared to equipotent doses of non-extra-fine aerosols. Extra-fine fixed combination of beclomethasone dipropionate and formoterol 100/6 mcg (FOSTER) was the first registered metered dose inhaler for the MART regimen in asthma. Key words: asthma, distal airways, inhalers, asthma control, exacerbation.

Divergent Chemo- and Biocatalytic Route to 16β-Methylcorticoids: Asymmetric Synthesis of Betamethasone Dipropionate, Clobetasol Propionate, and Beclomethasone Dipropionate.

16β-Methylcorticoids are among the most important glucocorticoid steroids for the treatment of various dermatological disorders, respiratory infections, and other allergic reactions elicited during inflammatory responses of the human body. Betamethasone dipropionate, clobetasol propionate, and beclomethasone dipropionate are particularly noteworthy for their synthetic intractability. Despite five decades of research, these 16β-methylcorticoids have remained challenging synthetic targets owing to insurmountable issues of reactivity, selectivity, and cost efficiency associated with all previously explored strategies. We herein report our practicability-oriented strategy toward the unified stereoselective synthesis of 16β-methylcorticoids in 12.6-14.0 % overall yield from commercially available 9α-hydroxyandrost-4-ene-3,17-dione (9α-OH-AD). In this approach, the chiral C16β-Me and C17α-OH groups of the corticosteroid D ring were installed via a substrate-controlled diastereo- and enantioselective Mn-catalyzed oxidation-reduction hydration of Δ4,9(11),16 -triene-3,20-dione. The C1-C2 double bond of the corticosteroid A ring was constructed using an unprecedented engineered 3-ketosteroid-Δ1 -dehydrogenase (MK4-KstD)-catalyzed regioselective Δ1 -dehydrogenation of Δ4,9(11) -diene-3,21-dione. This strategy provides a general method and a key precursor for the divergent synthesis of a variety of glucocorticoids and related steroidal drugs.

Divergent Chemo‐ and Biocatalytic Route to 16β‐Methylcorticoids: Asymmetric Synthesis of Betamethasone Dipropionate, Clobetasol Propionate, and Beclomethasone Dipropionate

Abstract16β‐Methylcorticoids are among the most important glucocorticoid steroids for the treatment of various dermatological disorders, respiratory infections, and other allergic reactions elicited during inflammatory responses of the human body. Betamethasone dipropionate, clobetasol propionate, and beclomethasone dipropionate are particularly noteworthy for their synthetic intractability. Despite five decades of research, these 16β‐methylcorticoids have remained challenging synthetic targets owing to insurmountable issues of reactivity, selectivity, and cost efficiency associated with all previously explored strategies. We herein report our practicability‐oriented strategy toward the unified stereoselective synthesis of 16β‐methylcorticoids in 12.6–14.0 % overall yield from commercially available 9α‐hydroxyandrost‐4‐ene‐3,17‐dione (9α‐OH‐AD). In this approach, the chiral C16β‐Me and C17α‐OH groups of the corticosteroid D ring were installed via a substrate‐controlled diastereo‐ and enantioselective Mn‐catalyzed oxidation‐reduction hydration of Δ4,9(11),16‐triene‐3,20‐dione. The C1−C2 double bond of the corticosteroid A ring was constructed using an unprecedented engineered 3‐ketosteroid‐Δ1‐dehydrogenase (MK4‐KstD)‐catalyzed regioselective Δ1‐dehydrogenation of Δ4,9(11)‐diene‐3,21‐dione. This strategy provides a general method and a key precursor for the divergent synthesis of a variety of glucocorticoids and related steroidal drugs.

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.

Integrated Analysis of the Effects of Cecal Microbiota and Serum Metabolome on Market Weights of Chinese Native Chickens.

The gut microbiota plays an important role in the physiological activities of the host and affects the formation of important economic traits in livestock farming. The effects of cecal microbiota on chicken weights were investigated using the Guizhou yellow chicken as a model. Experimental cohorts from chickens with high- (HC, n = 16) and low-market-weights (LC, n = 16) were collected. Microbial 16S rRNA gene sequencing and non-targeted serum metabolome data were integrated to explore the effect and metabolic mechanism of cecal microbiota on market weight. The genera Lachnoclostridium, Alistipes, Negativibacillus, Sellimonas, and Ruminococcus torques were enriched in the HC group, while Phascolarctobacterium was enriched in the LC group (p < 0.05). Metabolomic analysis determined that pantothenic acid (vitamin B5), luvangetin (2H-1-benzopyran-6-acrylic acid), and menadione (vitamin K3) were significantly higher in HC serum, while beclomethasone dipropionate (a glucocorticoid) and chlorophene (2-benzyl-4-chlorophenol) were present at higher levels in the LC group. The microbes enriched in HC were significantly positively correlated with metabolites, including pantothenic acid and menadione, and negatively correlated with beclomethasone dipropionate and chlorophene. These results indicated that specific cecal bacteria in Guizhou yellow chickens alter the host metabolism and growth performance. This study provides a reference for revealing the mechanism of cecal microbe actions that affect chicken body weight.

Stability assessment and content determination test of oral liquid forms of beclomethasone dipropionate prepared in hospital pharmacy

ObjectivesOral beclomethasone dipropionate (BDP) is known for its use as a therapeutic medicine for gastrointestinal graft-versus-host disease (GI-GVHD). Despite growing demand for oral BDP formulation, no commercial forms have yet...

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.

Comparison of Effects Beclomethasone Dipropionate with Flunisolide in Patients with Allergic Rhinitis

Objective: To compare the effectiveness of beclomethasone dipropionate with flunisolide given twice daily in terms of improvement in symptom score after 14 days of treatment in allergic rhinitis patients.Study Design: Quasi-Experimental Study.Place and Duration of Study: The study was carried out at the Department of ENT, PAF Hospital E-9 Islamabad, Pakistan, from January 2021 to July 2021.Materials and Methods: All patients of age 20-60 years of either gender having allergic rhinitis were included in the study. Allergic rhinitis was defined as any patient with a history of running nose with seasonal changes or exposure to allergens diagnosed by a consultant ENT surgeon. Patients with a history of smoking, asthma, having deviated nasal septum and inferior turbinate hypertrophy, patients already treated with Beclomethasone dipropionate or flunisolide, patients having an acute upper respiratory infection, and pregnant females were excluded from the study. A consecutive sampling technique was applied for the selection of participants. Patients were randomly divided into two groups: Group-A was given beclomethasone dipropionate, and Group-B Group-B was given flunisolide. The daily dose during treatment was 0.1 mg of beclomethasone dipropionate (50 ugs per puff) two-time each medicine daily. And dose of flunisolide nasal solution (flunisolide nasal spray 0.025%) flunisolide 50 micrograms in each nostril twice daily were 2 sprays (50 ugs) in each nostril 2 times a day: Treatment was continued for two weeks in each group. The symptoms score was estimated at baseline and after two weeks of intervention. Data were analyzed with the help of SPSS version 20.Results: The mean age of the study participants was 41.17+8.58 years in beclomethasone dipropionate and 41.85+8.52 years in flunisolide. Efficacy of flunisolide was significantly higher in terms of improvement in symptom score after 14 days of treatment in patients of allergic rhinitis compared to beclomethasone dipropionate (85% vs 79.58, p=0.035).Conclusion: Flunisolide inhaler is more effective when compared with beclomethasone dipropionate for treating allergic rhinitis.

BI26 Treatment-induced scleroderma in a patient with metastatic melanoma

Abstract We present a 71-year-old woman who presented with sclerodermoid plaques affecting the abdomen and lower limbs, following a single cycle of nivolumab and ipilimumab 20 months prior for BRAF-mutant metastatic melanoma (pulmonary and hepatic metastases). Immunotherapy was discontinued owing to iatrogenic colitis, confirmed on flexible sigmoidoscopy, and requiring oral prednisolone, infliximab and, later, modified-release beclomethasone dipropionate. Owing to the progression of hepatic disease, she was commenced on targeted therapy with dabrafenib and trametinib. A lesional punch biopsy was performed; histological analysis demonstrated a dense dermis with mild chronic inflammatory infiltrate, in keeping with a diagnosis of scleroderma. Treatment with a combination of topical corticosteroids and vitamin D analogues improved disease from 15% body surface area (BSA) to 3% after 4 months. We performed a literature search in PubMed for articles on immunotherapy-related scleroderma published up to August 2022 and identified 18 articles that met our inclusion criteria. Scleroderma was reported in patients with melanoma, non-small-cell lung cancer, renal cell carcinoma, rectal adenocarcinoma, adenocarcinoma of the lung and large-cell neuroendocrine lung cancer treated with pembrolizumab, nivolumab, atezolizumab and ipilimumab. Latency of onset ranged from 0 to 18 months, and treatment included topical and systemic corticosteroids, mycophenolate mofetil, hydroxychloroquine, cyclophosphamide, infliximab and immunoglobulins, with varying treatment outcomes. There was no clear relationship between cancer subtype, duration of treatment and response to treatment. Furthermore, the lack of documented quantitative or semiquantitative measurements for improvement such as BSA and modified Rodnan skin score is limiting. Our case report is important in promoting the awareness of localized scleroderma as a rare side-effect of immunotherapy and highlights the various treatment options available.

Comparison of Intranasal Steroid Application Using Nasal Spray and Spray-Sol to Treat Allergic Rhinitis: A Preliminary Investigation.

Allergic Rhinitis (AR) is a chronic inflammatory disease of sino-nasal mucosa, is IgE-mediated, and affects 10-40% of the global population. This study aimed to compare the efficacy of nasal administration of Beclomethasone Dipropionate (BDP) delivered via Spray-sol with nasal spray in patients suffering from AR. We included 28 AR patients assigned to one of the two following treatments: the Spray-sol group (BDP via Spray-sol) (n = 13) and the spray group (BDP using a common nasal spray) (n = 15). Both treatments were administered twice daily for 4 weeks. A nasal endoscopy evaluation and Total Nasal Symptom Score were performed at baseline and after treatment. The Spray-sol group showed better results than the spray group regarding nasal endoscopy (edema, p < 0.01; irritation, p < 0.01; secretion, p < 0.01) and nasal symptoms (nasal congestion, p < 0.05; rhinorrhea, p < 0.05; sneezing, p < 0.05; and total score, p < 0.05). No side effects were recorded. These data supported the fact that the use of BDP delivered with Spray-sol is more effective than BDP nasal spray in AR patients. Further studies are needed to confirm these encouraging results.

Sustained-Release Powders Based on Polymer Particles for Pulmonary Delivery of Beclomethasone Dipropionate in the Treatment of Lung Inflammation.

Inhaled corticosteroids are the mainstay in the management of lung inflammation associated to chronic lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Nonetheless, available inhalation products are mostly short-acting formulations that require frequent administrations and do not always produce the desired anti-inflammatory effects. In this work, the production of inhalable beclomethasone dipropionate (BDP) dry powders based on polymeric particles was attempted. As starting material, the PHEA-g-RhB-g-PLA-g-PEG copolymer was chosen, obtained by grafting 0.6, 2.4 and 3.0 mol%, respectively, of rhodamine (RhB), polylactic acid (PLA) and polyethylene glycol 5000 (PEG) on alpha,beta-poly(N-2-hydroxyethyl)DL-aspartamide (PHEA). The drug was loaded into the polymeric particles (MP) as an inclusion complex (CI) with hydroxypropyl-cyclodextrin (HP-β-Cyd) (at a stoichiometric ratio of 1:1) or as free form. The spray-drying (SD) process to produce MPs was optimized by keeping the polymer concentration (0.6 wt/vol%) constant in the liquid feed and by varying other parameters such as the drug concentration. The theoretical aerodynamic diameter (daer) values among the MPs are comparable and potentially suitable for inhalation, as confirmed also through evaluation of the experimental mass median aerodynamic diameter (MMADexp). BDP shows a controlled release profile from MPs that is significantly higher (more than tripled) than from Clenil®. In vitro tests on bronchial epithelial cells (16HBE) and adenocarcinomic human alveolar basal epithelial cells (A549) showed that all the MP samples (empty or drug-loaded) were highly biocompatible. None of the systems used induced apoptosis or necrosis. Moreover, the BDP loaded into the particles (BDP-Micro and CI-Micro) was more efficient than free BDP to counteract the effects of cigarette smoke and LPS on release of IL-6 and IL-8.

Residual Dipolar Coupling Based Conformational Analysis Allows the Configurational Assessment of Steroids with up to Eight Stereocenters.

Residual dipolar couplings (RDCs) induced by anisotropic media have been proved as a powerful tool for the structure elucidation of organic molecules in solution in nuclear magnetic resonance (NMR) based analysis. The value of dipolar couplings to solve complex conformational and configurational problems represents indeed an appealing analytical tool for the pharmaceutical industry particularly focusing on the stereochemistry characterization of NCEs since the early phase of the drug development process. In our work, RDCs were used for the conformational and configurational study of synthetic steroids with multiple stereocenters - prednisone and beclomethasone dipropionate (BDP) -. For both molecules the correct relative configuration was identified among all the possible diastereoisomers (32 and 128 respectively) arising from the compounds stereogenic carbons. Only for prednisone the use of additional experimental data (i. e. rOes) was necessary to resolve the right stereochemical structure.

Impact of dispersion media and carrier type on spray-dried proliposome powder formulations loaded with beclomethasone dipropionate for their pulmonary drug delivery via a next generation impactor.

Drug delivery via aerosolization for localized and systemic effect is a non-invasive approach to achieving pulmonary targeting. The aim of this study was to prepare spray-dried proliposome (SDP) powder formulations to produce carrier particles for superior aerosolization performance, assessed via a next generation impactor (NGI) in combination with a dry powder inhaler. SDP powder formulations (F1-F10) were prepared using a spray dryer, employing five different types of lactose carriers (Lactose monohydrate (LMH), lactose microfine (LMF), lactose 003, lactose 220 and lactose 300) and two different dispersion media. The first dispersion medium was comprised of water and ethanol (50:50% v/v ratio), and the second dispersion medium comprised wholly of ethanol (100%). In the first dispersion medium, the lipid phase (consisting of Soya phosphatidylcholine (SPC as phospholipid) and Beclomethasone dipropionate (BDP; model drug) were dissolved in ethanol and the lactose carrier in water, followed by spray drying. Whereas in second dispersion medium, the lipid phase and lactose carrier were dispersed in ethanol only, post spray drying. SDP powder formulations (F1-F5) possessed significantly smaller particles (2.89 ± 1.24-4.48 ± 1.20 μm), when compared to SDP F6-F10 formulations (10.63 ± 3.71-19.27 ± 4.98 μm), irrespective of lactose carrier type via SEM (scanning electron microscopy). Crystallinity of the F6-F10 and amorphicity of F1-F15 formulations were confirmed by XRD (X-ray diffraction). Differences in size and crystallinity were further reflected in production yield, where significantly higher production yield was obtained for F1-F5 (74.87 ± 4.28-87.32 ± 2.42%) then F6-F10 formulations (40.08 ± 5.714-54.98 ± 5.82%), irrespective of carrier type. Negligible differences were noted in terms of entrapment efficiency, when comparing F1-F5 SDP formulations (94.67 ± 8.41-96.35 ± 7.93) to F6-F10 formulations (78.16 ± 9.35-82.95 ± 9.62). Moreover, formulations F1-F5 demonstrated significantly higher fine particle fraction (FPF), fine particle dose (FPD) and respirable fraction (RF) (on average of 30.35%, 890.12 μg and 85.90%) when compared to counterpart SDP powder formulations (F6-F10). This study has demonstrated that when a combination of water and ethanol was employed as dispersion medium (formulations F1-F5), superior formulation properties for pulmonary drug delivery were observed, irrespective of carrier type employed.

Transport and deposition of beclomethasone dipropionate drug aerosols with varying ethanol concentration in severe asthmatic subjects

This study aims to assess the effects of varying an ethanol co-solvent on the deposition of drug particles in severe asthmatic subjects with distinct airway structures and lung functions using computational fluid dynamics. The subjects were selected from two quantitative computed tomography imaging-based severe asthmatic clusters, differentiated by airway constriction in the left lower lobe. Drug aerosols were assumed to be generated from a pressurized metered-dose inhaler (MDI). The aerosolized droplet sizes were varied by increasing the ethanol co-solvent concentration in the MDI solution. The MDI formulation consists of 1,1,2,2-tetrafluoroethane (HFA-134a), ethanol, and beclomethasone dipropionate (BDP) as the active pharmaceutical ingredient. Since HFA-134a and ethanol are volatile, both substances evaporate rapidly under ambient conditions and trigger condensation of water vapor, increasing the size of aerosols that are predominantly composed of water and BDP. The average deposition fraction in intra-thoracic airways for severe asthmatic subjects with (or without) airway constriction increased from 37%±12 to 53.2%±9.4 (or from 20.7%± 4.6 to 34.7%±6.6) when the ethanol concentration was increased from 1 to 10%wt/wt. However, when the ethanol concentration was further increased from 10 to 20%wt/wt, the deposition fraction decreased. This indicates the importance of selecting appropriate co-solvent amounts during drug formulation development for the treatment of patients with narrowed airway disease. For severe asthmatic subjects with airway narrowing, the inhaled aerosol may benefit from a low hygroscopic effect by reducing ethanol concentration to penetrate the peripheral region effectively. These results could potentially inform the selection of co-solvent amounts for inhalation therapies in a cluster-specific manner.

Efficacy and safety of oral beclomethasone dipropionate and budesonide MMX versus 5-aminosalicylates or placebo in ulcerative colitis: a systematic review and meta-analysis.

Low bioavailability steroids, including beclomethasone dipropionate (BDP) and budesonide MMX, have been developed to ensure colonic targeting and low systemic activity than systematic corticosteroids in treating patients with ulcerative colitis (UC). This systematic review and meta-analysis evaluated the efficacy and safety of BDP and budesonide MMX® compared with 5-aminosalicylic acid (5-ASAs) or placebo, in patients with mild-to-moderate UC. Systematic review and meta-analysis. We searched MEDLINE, EMBASE, and the Cochrane central register of controlled trials from inception to December 2021. We included all available randomized controlled trials (RCTs) comparing oral BDP or budesonide MMX with 5-ASAs or with placebo in induction of remission of mild-to-moderate UC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. We identified two RCTs comparing BDP 5 mg with 5-ASA, one RCTs comparing BDP 10 mg with 5-ASA, two RCTs BDP 5 mg versus placebo, one RCT BDP 10 mg versus placebo, two RCTs budesonide MMX 9 mg versus 5-ASA, and six RCTs budesonide MMX 9 mg versus placebo. In terms of achieving clinical remission or improvement, BDP 5 mg, BDP 10 mg, and budesonide MMX 9 mg were more effective than placebo (OR 2.36, 95% CI 1.37-4.08; OR 2.23, 95% CI 1.02-4.87; and OR 2.03, 95% CI 1.45-2.85, respectively). The drugs were also more effective than placebo in achieving endoscopic remission. Regarding the comparisons with 5-ASA, we found no differences between 5-ASA and BDP 5 mg or BDP 10 mg or budesonide MMX 9 mg in achieving clinical remission or improvement (OR 0.90, 95% CI 0.51-1.57; OR 1.54, 95% CI 0.42-5.64; and OR 1.17, 95% CI 0.82-1.66). However, 5-ASA was more effective than budesonide MMX 9 mg in achieving histological remission (OR 0.33, 95% CI 0.16-0.70). Overall, all the drugs were safe and well tolerated. Low bioavailability steroids were more effective than placebo in achieving clinical remission, clinical and endoscopic remission, and histological remission. No differences were found between 5-ASA and BDP or budesonide MMX. Surely, more RCTs, also comparing BDP and budesonide MMX, are mandatory to confirm or not these results.

Дисфункція дрібних дихальних шляхів та можливості її корекції при астмі

Abstract. Background. Although randomized controlled trials have shown that asthma control is an achievable goal, real-life studies over the past 20 years have shown that asthma remains poorly controlled in a significant proportion of patients, even among those receiving treatment at asthma specialist, and in patients with mild asthma who regularly take inhaled corticosteroids. Even when asthma control is achieved, it is not optimal on all GINA steps. The small airways have been recognized as the primary site of airflow limitation in asthma. The aim of the work: to study, according to the literature, the peculiarities of the dysfunction of the small airways in asthma and to evaluate the possibilities of its treatment. Materials and methods. Scientific articles that covered the pathophysiology of small airways disorders, their impact on asthma control, diagnostic methods, and pharmacological treatment methods were analyzed. The results. Airways with an internal diameter &lt; 2 mm, which do not contain cartilage in their walls and extend from the 8th generation of the airways to the periphery of the lung, are collectively called “small airways”. They are called the QUIET ZONE because they are difficult to assess and treat in patients with asthma who are not optimally controlled but have relatively normal FEV1 and disproportionate small airways dysfunction (SAD). Predominant in patients at all stages of treatment, associated with poor disease control. The ATLANTIS study showed that up to 91 % of patients with asthma have. The small airways have a high density of corticosteroid and β2-adrenoceptors, which means that they can be influenced. The main task is that the drugs should reach these small airways. Conventional inhalers that generate particles larger than 2 μm do not address the problem of SAD in patients with asthma. Inhaler devices that produce ultrafine particles of inhaled corticosteroids alone or in combination with long-acting β-agonists with a diameter of less than 2 μm have the potential to improve long-term asthma control along with a corresponding improvement in small airway function. The fixed combination of beclomethasone dipropionate with formoterol has optimal deposition in the respiratory tract — central pulmonary deposition accounts for 66 %, and peripheral — 34 % of the dose, thus the drug is delivered to both the central and peripheral respiratory tracts and affects inflammation and bronchoconstriction throughout the lungs. This is facilitated by MODULITE technology. The effectiveness and safety of the use of the BDP/F combination (Foster) in MART regimen is confirmed by a significant evidence base, which guaranteed its place in the Track1 treatment of asthma. Conclusions: Patients with asthma have a serious inflammatory process in the peripheral airways, which makes them the main site of obstruction in asthma; SAD predominates in patients at all stages of asthma, is associated with poor disease control, is responsible for air trapping, correlates with poor asthma control1, and predicts an increased risk of exacerbations in patients. The fixed combination of beclamethasone/formoterol in one inhaler (Foster) is the only extrafinely dispersed fixed combination of ICS/LABA that reaches the small airways; the fixed combination of BDP/Formoterol in the MART regimen provides a significant reduction in the frequency of severe complications, hospitalizations, emergency calls, and reduces the number of courses of systemic corticosteroids.

Beclomethasone dipropionate: efficacy and safety of the administration by nebulization.

The advent of inhaled corticosteroids (ICS) brought a revolution in the management of asthma, representing now the cornerstone in this pathological condition treatment. Indeed, these drugs have clearly shown to possess a high degree of both efficacy and safety. Beclomethasone dipropionate (BDP) is the first molecule tested in the early 1970s. When administered via nebulizers or pressurized metered-dose inhalers (pMDI), BDP was found to be effective in reducing the symptoms frequency and severity in asthmatic patients, even in those previously treated with low-dose oral corticosteroids. The drug was thus produced to be administered by nebulization or via pMDI. Nebulizers are a practical and efficient tool for administering inhaled drugs in patients of all degree of severity and belonging to all ages, but are especially useful for those unable to utilize other inhaler devices correctly. BDP aerosolization, when generated by modern pneumatic nebulizers, can deliver particles with a mass median aerodynamic diameter (MMAD) value of 2.9-3.7 µm. This ability allows the deposition of the drug in small caliber airways, and considerably reduces the amount of drug deposited in the oropharynx, thus improving this molecule pharmacokinetics. This review aims to analyze the factors influencing the efficacy and safety of ICS, evaluating in detail the characteristics of BDP administered by nebulization.