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Background: Intranasal corticosteroids (INCS) are used for several conditions, including allergic rhinitis and sinusitis. Consequently, their safety profile needs continuous monitoring. This study aimed to analyse the adverse drug reactions (ADRs) of the INCS with market authorisation in Europe. Methods: A retrospective analysis of the ADR data from EudraVigilance in the period between the 1 January 2011 and 12 June 2023 was performed, with 2641 reports selected for analysis. ADRs were categorised by seriousness and evolution, with a focus on the most prevalent ADRs and their alignment with the Summary of Product Characteristics (SmPC). Results: The 18–64 age group, particularly females, was most affected. Mometasone was the most reported INCS, with predominantly non-serious ADRs, evolving towards resolution, which often were not listed in the SmPC. From the reported ADRs that were not described in the SmPC of the INCS studied, "Anosmia" and "Ageusia" were highlighted. Regarding the ADRs described in the SmPC, the most frequently reported were "Epistaxis" and "Headache". The ADRs belonging to the Designated Medical Event list were also analysed, with "Angioedema" as the most reported ADR, which was mainly associated with budesonide. Conclusions: These findings underscore the importance of continuous INCS monitoring to mitigate ADRs and safeguard public health. Further research is warranted to explore potential novel signs for safety arising from previously unreported ADRs. [ABSTRACT FROM AUTHOR]

Background: Intranasal corticosteroids were recommended as first‐line drugs for the treatment of allergic rhinitis (AR) children. A variety of corticosteroids were available for clinical choice; however, which could relieve the clinical symptoms of patients to the greatest extent was currently unknown. Thus, we performed a network meta‐analysis (NMA) to systematically evaluate the effectiveness and safety of different corticosteroids in treating children with AR, which might provide a basis for more rational clinical treatment decisions. Methods: Seven electronic databases were searched, and the retrieval time range was the time from their inception to November 2023. The literature screening, data extraction, and assessment of the risk of bias of included studies were completed independently by two reviewers. A frequentist NMA was performed with Stata17.0 software. Results: A total of 43 RCTs covering 10,897 participants were included. In the improvement of reflective total nasal symptom score (rTNSS) and instantaneous total nasal symptom score (iTNSS), fluticasone furoate nasal spray (FFNS) and beclomethasone dipropionate (BDP) nasal aerosol presented the best efficacy. Regarding the incidence of adverse reactions, mometasone furoate aqueous nasal spray (MFANS) and BDP showed a good safety profile. In terms of the influence of cortisol (urinary free cortisol, plasma cortisol) and growth, no significant difference was observed between the different groups. Conclusion: The results showed that BDP nasal aerosol and FFNS had best efficacy; MFANS and BDP had the best safety profile. However, this conclusion was less convincing because of the limited numbers of patients/controls and study quality. [ABSTRACT FROM AUTHOR]

The present work is concerned with the novel, accurate, and precise quantification of beclomethasone dipropionate and fusidic acid in combination (cream), which was performed using high-performance thin-layer chromatography (HPTLC), and validation was performed based on International Council for Harmonization guidelines (Q2 R1). A series of HPTLC tests was conducted on pre-coated silica gel G60 F254 plates as the stationary phase and n-hexane:ethyl acetate:toluene:diethyl ether (4.5:5.5:1:0.2, v/v/v/v) as the mobile phase. Chamber saturation time was 30 min to attain the desired results. The Rf of beclomethasone dipropionate and fusidic acid was determined to be 0.52 and 0.36 respectively. The densitometric estimation was performed in reflectance mode at 238 nm. A linear relationship was seen in the range of 0.4–2.0 μg/band for beclomethasone dipropionate and 0.8–4.0 μg/band for fusidic acid with R2 of 0.9914 and 0.9927 for beclomethasone dipropionate and fusidic acid respectively. The limit of detection was found to be 0.2653 and 0.27040 for beclomethasone dipropionate and fusidic acid respectively, and the limit of quantification was found to be 0.42065 and 0.81940 for beclomethasone dipropionate and fusidic acid respectively. The percentage recovery was found to be within the range 98–102% for both beclomethasone dipropionate and fusidic acid. The method proposed was determined to be novel, error-free, robust, and reproducible. [ABSTRACT FROM AUTHOR]

Background: The extrafine single inhaler triple therapy (efSITT) containing beclomethasone dipropionate/formoterol fumarate/glycopyrronium 87/5/9 μg has proved to be efficacious in patients with chronic obstructive pulmonary disease (COPD) in randomized control trials. Objective: TRIWIN study evaluated the effectiveness of efSITT delivering beclomethasone dipropionate/formoterol fumarate/glycopyrronium 87/5/9 μg in COPD patients previously treated with multiple-inhaler triple therapy (MITT) in a real-world study in Greece. Design: Prospective, multicenter, observational, non-interventional study was conducted over 24 weeks. Methods: A total of 475 eligible patients had moderate-to-severe COPD, an indication for treatment with efSITT, and were symptomatic despite receiving MITT. COPD Assessment Test (CAT) score, pulmonary function parameters, use of rescue medication, and adherence to inhaler use were recorded at baseline (Visit 1), 3 (Visit 2), and 6 months (Visit 3) after treatment. Results: Mean CAT score decreased from 21.4 points at Visit 1, to 16.6 at Visit 2 and 15.1 at Visit 3 (p < 0.001 for all pair comparisons). At Visit 3, 79.8% of patients reached a CAT improvement exceeding minimal clinically important difference (⩾2), compared to baseline. Mean forced expiratory volume in 1 s (%pred.) increased from 55.4% at Visit 1 to 63.5% at the end of study period (p < 0.001), while mean forced vital capacity (%pred.) increased from 71.1% at Visit 1, to 76.7% at Visit 3 (p < 0.001). The mean Test of Adherence to Inhalers score increased from 42.5 to 45.3 and 46.3 points, for the three visits, respectively (p < 0.001 comparing Visits 1/2 and Visits 1/3; p = 0.006 comparing Visits 2/3). The percentage of patients showing good adherence rose from 33.7% at baseline to 58.3% at Visit 3. The percentage of patients using rescue medication during the last month dropped from 16.2% to 7.4% at the end of study period (p < 0.001). Pulmonary function parameters also improved. Conclusion: The TRIWIN results suggest that extrafine beclomethasone dipropionate/formoterol fumarate/glycopyrronium is effective in improving health status, pulmonary function, and adherence and in reducing rescue medication use in COPD patients previously treated with MITT, in a real-world setting in Greece. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop and validate a robust reversed‐phase high‐performance liquid chromatography (RP‐HPLC) method for the simultaneous estimation of neomycin sulfate (NEO) and beclomethasone dipropionate (BECLO) in both bulk drug and pharmaceutical dosage forms. The analysis was conducted using the Box‐Behnken design. The separation of NEO and BECLO was conducted on a Phenomenex Luna C‐18 column (4.6 × 150 mm, 5 µm), employing a mobile phase comprising a mixture of methanol and trifluoroacetic acid in a ratio of 88:12% v/v. The separation was performed at a flow rate of 0.6 mL/min. NEO and BECLO were analyzed at a wavelength of 240 nm employing a photodiode array detector. The validation of the methodology followed the guidelines outlined in the International Council for Harmonization Q2 R (1). The validation process involved assessing critical parameters such as linearity, accuracy, system suitability, precision, and robustness. The results for each parameter were found to be within the acceptable range. The results indicate that the established RP‐HPLC method can effectively be employed for the routine analysis of NEO and BECLO in bulk drug and pharmaceutical dosage forms. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

The introduction of inhaled corticosteroids (ICSs) changed over a few decades the treatment focus of mild-to-moderate asthma from bronchodilation to reduction in inflammation. This was achieved by inhaling a suitable corticosteroid (CS), giving a high, protracted airway concentration at a low total dose, thereby better combining efficacy and tolerance than oral therapy. Successful trials with the potent, lipophilic "skin" CS beclomethasone dipropionate (BDP) paved the way, suggesting that ICSs require a very low water solubility, prolonging their intraluminal dissolution within airways. The subsequent ICS development, with resulting clinical landmarks, is exemplified here with budesonide (BUD), showing that a similar efficacy/safety relationship is achievable by partly alternative mechanisms. BUD is much less lipophilic, giving it a 100-fold higher water solubility than BDP and later developed ICSs, leading to its more rapid intraluminal dissolution and faster airway and systemic uptake rates. In airway tissue, a BUD fraction is reversibly esterified to intracellular fatty acids, a lipophilic conjugate, which prolongs airway efficacy. Another mechanism is that the rapidly absorbed bulk fraction, via short plasma peaks, adds anti-inflammatory activity at the blood and bone marrow levels. Importantly, these plasma peaks are too short to provoke systemic adverse actions. Controlled clinical trials with BUD changed the use of ICS from a last resort to first-line treatment. Starting ICS treatment immediately after diagnosis ("early intervention") became a landmark for BUD. An established dose response made BUD suitable for the treatment of patients with all degrees of asthma severity. With the development of the budesonide/formoterol combination inhaler (BUD/FORM), BUD contributed to the widely used BUD/FORM maintenance and reliever therapy (MART). Recent studies demonstrated the value of BUD/FORM as a generally recommended as-needed therapy for asthma ("anti-inflammatory reliever", AIR). These abovementioned qualities have all influenced international asthma management and treatment guidelines. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In recent years, some new concepts have been added to asthma treatment such as "anti-inflammatory reliever" (β2-agonist use associated to an inhaled corticosteroid (ICS) as a reliever treatment) that combines the benefits of both therapies and provides short- and long-term benefits for treatment in asthma patients. Robust evidence has been presented in patients over 12 years, and the main changes in the international guidelines for asthma treatment were originally made in this age group. However, a few suggestions have been added to treatments in younger patients, in part because of the scarce evidence that exists in this group. We aim to analyze the information regarding the utilization of ICS + fast-acting beta-agonist (FABA) combination in children between 6 and 11 years. Although up until today only three published trials exist (two studies use beclomethasone + albuterol and one study uses budesonide + formoterol), they provide significant information on the benefits of ICS + FABA use in this population. [ABSTRACT FROM AUTHOR]

Dry powder inhalers (DPIs) have gained increasing clinical acceptance in the local treatment of lung diseases due to their ability to meet the evolving needs of patients while avoiding environmental concerns. However, some formulations for DPIs still encounter performance limitations in terms of aerodynamic properties and achievement of therapeutic doses. Innovative aerogel powder formulations for DPIs processed using combined supercritical CO2 (scCO2)-based technologies can overcome these limitations, especially in the case of poorly water-soluble drugs. The loading of hydrophobic drugs into aerogels can be optimized through a thorough understanding of the physicochemical properties of the formulation and the scCO2 processing conditions. In this study, drug-loaded alginate aerogel particles were prepared by combining gelation-emulsification techniques and scCO2-based technologies. Beclomethasone dipropionate (BDP), a hydrophobic corticosteroid, was incorporated into the aerogel matrix by scCO2 impregnation. The influence of contact time, initial amount of drug, and use of co-solvents on the efficiency of scCO2 impregnation were studied. The kinetics of the BDP adsorption process was modelled to elucidate the time required for the drug to attain equilibrium concentration under specific operating conditions. Nitrogen adsorption-desorption and helium pycnometry revealed particles with large surface area (>200 m2/g) and porosity (ca. 90%). The resulting aerogels had excellent aerodynamic properties at relevant BDP doses, as confirmed by in vitro lung deposition tests. Ex vivo permeability tests with porcine lung tissues evidenced that BDP released from the inhaled formulation could penetrate the bronchial tissue.

Background: 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). Objectives: 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. Design: Systematic review and meta-analysis Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Medical composites derived from Gamma-cyclodextrin (γ-CD) and beclomethasone dipropionate−gamma-cyclodextrin (BDP−γ-CD) are synthesized over supercritical-assisted atomization (SAA) herein. Carbon dioxide, which serves the dual function of spraying medium and co-solute, is incorporated in this process along with the ethanolic solvent. Results indicate that, for fine spherical particles, optimized aerosol performance could be obtained with 50.0% (w/w) ethanolic solvent, precipitator, and saturator at 373.2 K and 353.2 K, respectively, and carbon dioxide-to-γ-CD flow ratio of 1.8 in the presence of 10 wt% leucine (LEU) as dispersion enhancer. It is also noted that γ-CD solution at low concentration typically renders better aerosol performance of the particles. During drug particle-derivation, the solubility of drug BDP elevated considerably due to the formation of inclusion complexes, further assisted by the ethanolic solvent which increases the lipophilicity of BDP. Meanwhile, the in vitro aerosolization and dissolution performance of drug composites derived from varied γ-CD-to-BDP mass ratio (Z) were also evaluated. It was found that high Z promises higher fine particle fraction in the obtained drug composite while the dissolution rate of active ingredient (BDP) exhibits positive correlation to the content of water-soluble excipient (γ-CD) in the formulation. This study offers a new avenue for instant drug formulation with promising pulmonary delivery over the SAA technique. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Peristomal skin complications (PSCs) are relatively common in ostomy patients, particularly in those with ileostomies. Non-healing irritation presents a clinical challenge and leads to pain and impaired quality of life for patients. Methods: The cases of four ileostomy patients experiencing severe, challenging PSCs refractory to appliance changes, conventional dressings and barrier creams are discussed. Findings: The cases of one male and one female patient with an end ileostomy post-subtotal colectomy for ulcerative colitis, one female with a defunctioning ileostomy post-anterior resection for sigmoid carcinoma and one male with an end ileostomy with a complex Crohn's surgical history are described. Two puffs of a 250 mcg metered dose beclometasone inhaler were applied to the affected skin once or twice daily. Treatment ranged from 6 to 21 days. Complete resolution was seen in all cases. Conclusion: Topical use of a beclometasone inhaler was effective for severe peri-ileostomy PSC secondary to four different aetiologies. Further studies are warranted to determine the effectiveness of this treatment in a larger patient cohort. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Between 1986 and 2020 the Food and Drug Administration (FDA) approved fifty-three brand-name inhalers for asthma and chronic obstructive pulmonary disease (COPD), but by the end of 2022 only three of those inhalers faced independent generic competition. Manufacturers of brand-name inhalers have created long periods of market exclusivity by obtaining multiple patents, many on the delivery devices rather than the active ingredients, and by introducing new devices that contain old active ingredients. Limited generic competition for inhalers has raised questions about whether the Drug Price Competition and Patent Term Restoration Act of 1984, also known as the Hatch-Waxman Act, for challenging patents is adequately facilitating the entry of complex generic drug-device combinations. For the fifty-three brand-name inhalers approved during the period 1986-2020, generic manufacturers filed challenges authorized by the Hatch-Waxman Act, which are known as paragraph IV certifications, on only seven products (13 percent). The median time from FDA approval to first paragraph IV certification was fourteen years. Paragraph IV certifications resulted in approved generics for only two products, each of which experienced fifteen years of market exclusivity before generic approval. Reform of the generic drug approval system is critical to ensuring the timely availability of competitive markets for generic drug-device combinations such as inhalers. [ABSTRACT FROM AUTHOR]

BACKGROUND: COPD is characterized by progressive and irreversible air flow limitations. Single-inhaler therapies (SITTs) incorporating an inhaled corticosteroid, a long-acting muscarinic antagonist, and a long-acting β2-agonist have been shown to effectively alleviate symptoms and improve lung function. Fluticasone-furoate/umeclidinium/vilanterol (F/U/V) and budesonide/glyco-pyrronium/formoterol (B/G/F) are available as SITT in Japan. However, the clinical differences between these 2 combinations and the predictors of their proper use have not been established. This study aimed to identify the subject characteristics that could predict the effectiveness of inhaler therapy. METHODS: We assessed the pulmonary function test results of subjects with COPD before and one month after using F/U/V and B/G/F as SITT. Subjects with a difference of 100 mL or more in the FEV1 after treatment with pre-SITT were extracted and divided into the F/U/V effect and no-effect group and B/G/F effect and no-effect group to examine the factors associated with positive outcomes with each inhaler. RESULTS: F/U/V and B/G/F significantly improved the inspiratory capacity (IC), %IC, FVC, and %FEV1 when compared to pre-inter-vention values (P < .001, P = .001, P = .007, P = .009, respectively, for F/U/V; and P = .006, P = .008, P = .038, P = .005, respectively, for B/G/F). Factors associated with FEV1 improvement in F/U/V included lower %IC (odds ratio 0.97 [95% CI 0.94-0.99], P = .03) and a higher modified Medical Research Council (mMRC) dyspnea score (2.36 [1.27-4.70], P < .01). In addition, a higher %IC (1.03 [1.00-1.06], P = .02) and lower mMRC dyspnea score (0.55 [0.28-0.99], P = .041) were predictors for the effectiveness of B/G/F. CONCLUSIONS: Our results showed that SITT significantly improved the IC, %IC, FVC, and %FEV1 when compared to pre-inter-vention and that F/U/V was more effective in subjects with severe symptoms, whereas B/G/F was more effective in subjects with mild symptoms. [ABSTRACT FROM AUTHOR]

Background: The small airway disease has been recognized as a central feature of chronic obstructive pulmonary disease (COPD). Triple fixed combination beclomethasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) is provided as a pressurized single-dose inhaler based on an extra-fine formulation, which has been approved for patients with COPD experiencing frequent disease exacerbations. Methods: The aim of our real-life single-center observational study was to investigate, in 22 patients with COPD, the effects of BDP/FF/G on lung function, respiratory symptoms, health status, and exacerbation rate. Several clinical and lung functional parameters were evaluated at baseline and after 12 months of treatment with combined inhaled triple therapy. Results: With respect to baseline, after 12 months of treatment with BDP/FF/G, significant changes were recorded with regard to forced expiratory flow at 75% of forced vital capacity (FVC) (p < 0.01), forced expiratory flow at 50% of FVC (p < 0.01), forced expiratory flow at 25% of FVC (p < 0.05), and forced mid-expiratory flow between 25% and 75% of FVC (p < 0.01). Moreover, we observed reductions of total resistance (p < 0.01), effective resistance (p < 0.01), and effective specific resistance (p < 0.01). In the same period, residual volume diminished (p < 0.01) and forced expiratory volume in 1 s increased (p < 0.01). Moreover, in a subgroup of 16 patients, an enhancement of diffusion lung capacity (p < 0.01) was also detected. These functional results were paralleled by concomitant clinical effects, as evidenced by the improvements of modified British Medical Research Council (mMRC) dyspnea scale (p < 0.001), COPD Assessment Test (CAT) score (p < 0.0001), and COPD exacerbations (p < 0.0001). Conclusion: In conclusion, the valuable findings of our observational study consist in the corroboration in a real-life context of the therapeutic effects evidenced by randomized controlled trials with regard to the use of the triple inhaled BDP/FF/G therapy in patients with COPD. [ABSTRACT FROM AUTHOR]

Hand eczema is a common disease – up to 5% in the general population. In addition, eczema is closely related to atopy and, like atopic dermatitis, to a mutation in the FLG gene. In addition to genetic factors, eczema is caused by external irritants and toxic substances. Eczema often occurs in families with atopic diseases, including asthma, allergic rhinitis/hay fever (and food allergies), and atopic dermatitis. These diseases share a common pathogenesis and often occur together in the same person and/or family. Eczematous rashes are often accompanied by itching. This symptom can lead not only to sleep disturbances but also to secondary infections. According to some data, the rate of infections in eczema can be more than 70%. In such cases, the drugs of choice are combined glucocorticosteroids (GC), which in addition to GC contain an antimycotic and an antibiotic. Our practical experience shows the high effectiveness of the combination of beclomethasone dipropionate, gentamicin, and clotrimazole not only in cases of eczema complicated by secondary infection but also in patients with other infected chronic dermatoses. This article reviews these and other practical aspects and problems in the treatment of hand eczema, discusses the etiological factors that lead to the development of the disease, and presents current data from clinical recommendations and guidelines for the treatment of eczema.

Skin psoriasis is defined as receiving external stimulation to activate skin dendritic cells (DCs) which can release interleukin 23 (IL-23) to interlink the innate and adaptive immunity as well as induce T helper 17 (Th17) cell differentiation leading to elevated production of interleukin 17 (IL-17) for keratinocytes over production. This autoimmune loop in psoriasis pathogenesis is influenced by G protein-coupled receptor (GPCR) signalling transduction, and in particular, function of adhesion molecule GPR97 in psoriasis endures to be utterly addressed. In this research, our team allocated GPR97 depletion (GPR97-/-), GPR97 conditional depletion on dendritic cell (DC-cKO), and keratin 14-conditional knockout (K14-cKO) mice models to explore the function of GPR97 which influences keratinocytes and skin immunity. It was found that significantly aggravated psoriasis-like lesion in GPR97-/- mice. In addition, hyperproliferative keratinocytes as well as accumulation of DCs and Th17 cells were detected in imiquimod (IMQ)-induced GPR97-/- mice, which was consistent with the results in DC-cKO and K14-cKO psoriasis model. Additional investigations indicated that beclomethasone dipropionate (BDP), an agonist of GPR97, attenuated the psoriasis-like skin disease and restricted HaCaT cells abnormal proliferation as well as Th17 cells differentiation. Particularly, we found that level of NF-κB p65 was increased in GPR97-/- DCs and BDP could inhibit p65 activation in DCs. Role of GPR97 is indispensable and this adhesion receptor may affect immune cell enrichment and function in skin and alter keratinocytes proliferation as well as differentiation in psoriasis. [Display omitted] • GPR97 regulates DC activation and following Th17 cell differentiation. • Beclomethasone dipropionate significantly restrict psoriasis pathogenesis via GPR97. • GPR97 deletion activate NF-kB signalling pathway leading to psoriatic aggravation. [ABSTRACT FROM AUTHOR]

Aim: To evaluate if hyaluronic acid reduces proctitis episodes with respect to corticosteroids in prostate cancer patients submitted to radical or adjuvant radiotherapy. Methods: A consecutive series of eligible patients received hyaluronic acid enemas as supportive care (experimental group, from January 2013 to June 2015). A historical group (control group), treated from October 2011 to December 2012, received beclomethasone dipropionate suppositories. We registered each patient’s data regarding acute and chronic proctitis. All patients were treated with static-intensity-modulated radiotherapy coupled to a daily set-up verification with orthogonal anterior–posterior/lateral X-ray pairs. Results: A total of 269 patients, 175 in the experimental group and 94 in the control group, was evaluated; 2 Gy/day (up to a total median dose of 80 Gy) and 2.7 Gy/day (up to a total median dose of 67.5 Gy) fractionation schemes were used for 216 and 53 patients, respectively. All patients had a good tolerance to radiotherapy, reporting no G3 or greater proctitis. No significant difference was reported concerning the total rate of proctitis between the two groups but only with respect to its grade: a higher G2 rate within the control group. There was no correlation between daily dose fractionation and toxicity grade. Conclusions: Hyaluronic acid enemas might be effective in reducing the severity of radiation proctitis.

Objective: To develop a validated analytical method for simultaneous estimation of Fusidic acid and Beclomethasone dipropionate in pharmaceutical combined dosage form by HPLC. Method: A HPLC method was developed and validated for assay of Fusidic acid (FA) and Beclomethasone dipropionate (BD) in Topical pharmaceutical formulation. The chromatographic separation was achieved on Kromasil C18, 5µm (125 X 4.6 mm) column at ambient temperature of 250C, at a flow rate 2.5 mL/min using LC-2010 CHT Liquid Chromatography, Shimadzu HPLC system. Different mobile phases were used on trial and error basis for separation of two drugs. The final mobile phase selected for analysis comprised of mixture of Methanol, Ortho-Phosphoric acid and Acetonitrile in the ratio of 10:45:45% (v/v/v). Both the drugs showed maximum absorbance at 220 nm which was selected as the wavelength of detection throughout the experimental work. Validation of developed method was carried out according to ICH guidelines. Result: HPLC method was successfully developed for separation of FA and BD with good resolution. Method validation after assessment of various parameters indicated low % RSD within an acceptable limit of < 2.0%. Conclusion: The developed HPLC method for estimation of FA and BD is rapid, reliable, precise, and reproducible. [ABSTRACT FROM AUTHOR]