Budesonide Research Articles

Efficacy of Pulmicort Respules Combined with Azithromycin in the Treatment of Children with Recurrent Respiratory Tract Infection Caused by Mycoplasmal Pneumonia.

Aims/Background The drug treatment of recurrent respiratory tract infection caused by mycoplasma pneumonia (MP) has a complex background, involving the characteristics of pathogens, drug resistance, and multiple treatment methods. This study aimed to analyze the therapeutic effect of pulmicort respules and azithromycin on children with recurrent respiratory tract infection caused by MP. Methods The clinical data of 106 children with recurrent respiratory tract infection caused by MP diagnosed in Huoqiu First People's Hospital from July 2021 to July 2023 were retrospectively analyzed. Based on different therapeutic methods, 56 children treated with azithromycin were included in the reference group, and 50 children treated with pulmicort respules and azithromycin were included in the observation group. The disappearance time of clinical symptoms, levels of inflammatory factors, immunoglobulin levels, and complications in both groups were observed and compared. Results After treatment, the disappearance time of fever, cough, pulmonary rales, and expectoration was shorter in the observation group, compared with the reference group (p < 0.001). No significant difference was observed in levels of tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), or interleukin-6 (IL-6) between the two groups on the first day of admission (p > 0.05). After 1 week of treatment, the observation group had significantly higher levels of TNF-α, IL-2, and IL-6 compared with the reference group (p < 0.05). No significant difference was observed in levels of immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) between the two groups on the first day of admission (p > 0.05). After 1 week of treatment, the observation group had significantly lower levels of IgG, IgA, and IgM than the reference group (p < 0.01). This study revealed that the incidence of complications in the observation group was 16.00%, which was significantly lower than the 37.50% in the reference group (p < 0.05). Conclusion In the short-term clinical treatment, the combination application of pulmicort respules and azithromycin can effectively improve the immune function of children with recurrent respiratory tract infection caused by MP and relieve their clinical symptoms.

Alanyl-Glutamine Inhibits the Epithelial-Mesenchymal Transition of Airway Epithelial Cells in Asthmatic Mice via DPP4-SIRT1 Pathway

Introduction: Alanyl-glutamine (Ala-Gln) is a compound known for its protective effects in various tissue injuries. However, its role in asthma-related lung injuries remains underexplored. This study investigates the mechanisms by which Ala-Gln modulates sDPP4-induced airway epithelial-mesenchymal transition and ovalbumin (OVA)-induced asthma in a mouse model. Methods: An asthma model was established in female C57BL/6 J mice by using OVA. CD4+ T cells and bronchial epithelial cells (BECs) were isolated from the spleen and bronchi of the mice, respectively. Interventions included recombinant sCD26/sDPP4 protein, Ala-Gln, and EX527 (a SIRT1 inhibitor). Flow cytometry was used to assess Th17 and Treg cell populations. Mice were treated with Ala-Gln, EX527, and budesonide (BUD). Histopathological changes in lung tissues were evaluated using hematoxylin-eosin and Masson staining. White blood cell counts were measured with a hematology analyzer. The expression levels of DPP4, IL-17, SIRT1, SMAD2/3, N-cadherin, E-cadherin, MMP9, and α-SMA proteins were analyzed. Results: Treatment with recombinant sCD26/sDPP4 resulted in decreased E-cadherin expression in BECs and increased levels of α-SMA, MMP9, and N-cadherin, effects that were mitigated by Ala-Gln. Ala-Gln also prevented the reduction in SIRT1 expression in BECs and the increase in Th17 cell differentiation induced by recombinant sCD26/sDPP4. EX527 administration alongside Ala-Gln reversed these changes and enhanced the phosphorylation of SMAD2/3 through SIRT1 signaling. BUD alone reduced inflammation and fibrosis in bronchial tissue and lowered the Th17/Treg ratio in peribronchial lymph nodes. The therapeutic effect of BUD was further improved with concurrent Ala-Gln treatment. Conclusion: Ala-Gln can inhibit BEC fibrosis and Th17 cell differentiation mediated by recombinant sCD26/sDPP4 through the SIRT1 pathway. Combined with BUD, Ala-Gln enhanced therapeutic efficacy in OVA-induced asthma in mice, which could offer improved outcomes for asthmatic patients with elevated DPP4 levels.

Locally Acting Budesonide-Loaded Solid Self-Microemulsifying Drug Delivery Systems (SMEDDS) for Distal Ulcerative Colitis.

Budesonide (BUD) is a BCS class II medication with poor water solubility and limited oral bioavailability. In this study, innovative solid self-microemulsifying drug delivery systems (BUD-SMEDDS) were developed for effective local management of distal ulcerative colitis (UC). Based on solubility and emulsification tests, the components of the self-microemulsifying drug delivery system (SMEDDS) were Capryol™ 90, Tween 80, and Transcutol HP. The impacts of BUD-SMEDDS ingredients (as inputs) on the average globule size (AGS), polydispersity index (PDI), and self-emulsification time (SET) as responses were investigated using the Box-Behnken design methodology. Solid rectal systems were then fabricated using the optimized values of SMEDDS components in Lutrol® bases. The developed systems were evaluated for in vitro characteristics and in vivo efficacy using a rat colitis model. For all responses, the greatest impact was attributed to the oil content of SMEDDS. An optimized BUD-SMEDDS with AGS of 33 ± 2.9 nm, PDI of 0.29 ± 0.03 and SET of 25 ± 2.5 s) was selected for rectal formulations. The developed formulations demonstrated acceptable physical characteristics and mucoadhesive abilities. Differential scanning calorimetric (DSC) analysis revealed the absence of BUD crystallinity in the SMEDDS formulations. The drug release patterns could be regulated by selecting the grade and composition of the incorporated Lutrols. Clinical and histopathological assessments revealed considerable improvements in animals treated with BUD-SMEDDS formulations. Overall findings confirmed the superior capability of solid SMEDDS as BUD carriers to manage distal colitis in tested animals.

Formulation and evaluation of carrier-based dry powders containing budesonide and arformoterol for inhalation therapy

Asthma and Chronic Obstructive Pulmonary Disease (COPD) are major global health concerns, with inhalation therapy being a primary treatment method. Dry powder inhalers (DPIs) often face challenges related to particle aggregation, which can diminish drug delivery efficiency. This study investigates particle aggregation and aims to optimize the cohesion–adhesion balance to improve inhalation efficiency. Advanced techniques like atomic force microscopy and Raman imaging were used to analyze particle interactions, focusing on lactose ratios, particle morphology, and drug-drug interactions. The therapeutic efficacy of optimized formulations containing budesonide (BUD) and Arformoterol (AFT) was assessed using an asthma model, showing significant improvements in sRAW, neutrophil count, and tidal volume compared to the positive control, with p-values below 0.01. AFT exhibited comparable efficacy to Formoterol at half the dose. Additionally, pharmacokinetic studies demonstrated similar in vivo behavior between the drugs, confirming the therapeutic advantage of AFT, with p-values for AUC0−t and Cmax of .646 and .153, respectively. The fine particle fractions for AFT and BUD were 39.4% and 50.6%, respectively, indicating improved drug delivery efficiency and potential for better clinical outcomes in asthma and COPD patients.

The Design of Novel 3D-Printed, Moulded, and Oral Viscous Budesonide Formulations for Paediatrics: A Comparative Evaluation of Their Mucoadhesive Properties.

Paediatric eosinophilic oesophagitis (EoE) treatment is challenging due to the limited number of age-appropriate formulations. This study aims to develop and evaluate oral viscous suspensions and solid formulations of budesonide (BUD), focusing on their in vitro mucoadhesive properties, to enhance drug delivery and therapeutic outcomes in paediatric EoE. This study encompasses the development of oral viscous suspensions and orodispersible solid formulations (moulded tablets and 3D-printed dosage forms) containing BUD. The formulations underwent quality control tests as per the European Pharmacopoeia, chemical stability assessments, and an in vitro evaluation of their mucoadhesiveness properties. A validated analytical method enabled accurate BUD quantification and efficient extraction, and all developed formulations demonstrated chemical stability for 30 days, meeting Ph. Eur. quality standards. Three-dimensional printing using SSE successfully produced 1 mg and 0.5 mg BUD printlets, complying with quality tests for conventional tablets. Formulations containing xanthan gum (L2-XG and P1-0.5-XG) exhibited superior mucoadhesive properties. L2-XG showed significantly higher mucoadhesion than L1-MC. Among the solid formulations, P1-0.5-XG demonstrated the highest mucoadhesive properties. This is the first study to develop solid oral dosage forms of BUD at a very low dose, specifically for paediatric use. The results highlight the potential of 3D printing for developing individualised orodispersible BUD formulations with improved bioadhesion for paediatric EoE treatment. The L2-XG formulation and the XG-containing printlets are the most promising formulations in terms of increasing contact time with the oesophageal mucosa, which could translate into improved therapeutic efficacy in this patient population.

Experimental measurement, thermodynamic analysis, and mathematical modeling for budesonide solubility in 1-propanol + water mixtures at T = (293.2 to 313.2) K.

Budesonide (BDS) a steroid-based anti-inflammatory drug widely prescribed for various diseases, has a low aqueous solubility. In this study, we investigated cosolvency approach to study the thermodynamic specifications related to the solubility of BDS at the temperature range of 293.2-313.2K in (1-propanol + water) mixtures applying the shaking flask method. The predictive power of different mathematical models for experimental data in the cosolvency systems was evaluated. For this purpose, the linear and nonlinear mathematical equations such as van't Hoff model (as a linear model), Buchowski-Ksiazczak equation (as a non-linear), CNIBS/R-K and MRS models (as a linear model for solvent composition at an isothermal condition), modified Wilson model (as a non-linear model for isothermal condition), the Jouyban-Acree model (as a model that considers temperature and solvent composition), and Jouyban-Acree-van't Hoff model (as a model with no further input data) were studied. Also, the Williams-Amidon excess Gibbs energy model was investigated. In addition, the related apparent thermodynamics of the BDS dissolution process in the desired temperature such as Gibbs free energy, enthalpy, and entropy, were computed by the corresponding equations. Moreover, based on the inverse Kirkwood-Buff integrals, it is demonstrated that BDS is preferentially solvated by water in water-rich mixtures. The accuracy of the fitness was evaluated with mean relative deviations (MRDs%) for back-calculated molar BDS solubility data. The result showed that the maximum solubility of BDS was obtained at 0.7 mass fraction of 1-propanol at all temperatures. Thermodynamic studies demonstrated that BDS dissolution procedures were obtained as endothermic and entropy-driven in almost all cases. The overall MRDs% values for the back-computed BDS solubility in the aqueous mixture of 1-propanol based on van't Hoff model, Buchowski-Ksiazczak equation, CNIBS/R-K model, modified Wilson model, Jouyban-Acree model, Jouyban-Acree-van't Hoff model, MRS model, and Williams-Amidon excess Gibbs energy model were found 1.93%, 1.80%, 11.68%, 33.32%, 12.30%, 9.24%, 10.70%, and 6.57%, respectively.

Inhaled budesonide and pulmonary sarcoidosis revisited.

Results of a few controlled clinical studies have been reported with inhaled corticosteroids (ICS) in patients with pulmonary sarcoidosis. Some evidence of efficacy has been observed, but mainly with the ICS budesonide (BUD). These clinically important and statistically significant results are restricted to maintenance therapy with BUD after induction of treatment with systemic corticosteroids for a few weeks or months. Positive results have also been described in patients with relapses after earlier treatment with oral corticosteroids. A possible explanation for BUD's efficacy in patients with parenchymal lesions could be that inhaled BUD is rapidly absorbed into systemic circulation, creating plasma peaks which result in systemic anti-inflammatory activity in both peripheral airways and lung tissue. At airway level this steroid activity is furthermore prolonged because a BUD fraction is intracellularly, reversibly transformed into lipophilic BUD-oleate. These mechanisms have been proposed to explain the theoretically unexpected similar efficacy of BUD compared with more lipophilic ICSs in patients with asthma and COPD. In this review we summarize the results of clinical studies with ICSs in patients with pulmonary sarcoidosis. It is obvious that current ICSs, including BUD, cannot generally be recommended as such for treatment of sarcoidosis. However, using BUD as a model substance further pharmacologic and kinetic studies could possibly define a kinetic profile giving optimal partitioning between airway and systemic activity with less adverse systemic risks. Such a substance could replace or reduce oral corticosteroids in the treatment of airway and pulmonary parenchymal diseases.

Clinical Efficacy of Spleen Aminopeptide Combined with Budesonide and Levosalbutamol Hydrochloride, and Its Effects on Inflammatory Markers and Immune Function in Pediatric Bronchial Asthma

Background: Bronchial asthma (BA) is a heterogeneous disease characterized primarily by chronic airway inflammation and airway hyperresponsiveness (AHR). Objectives: This was a retrospective study aimed at exploring the clinical efficacy of spleen aminopeptide (SA) combined with budesonide (BUD) and levosalbutamol hydrochloride (LEV) as a therapy for pediatric BA, and to observe its effects on inflammatory markers and immune function. Methods: From June 2022 to June 2023, eighty individuals diagnosed with BA were divided into two groups: A control group and an observation group, based on different therapeutic methods. The control group received inhalation therapy with nebulized BUD and LEV, while the observation group received the same inhalation therapy as the control group, along with SA oral lyophilized powder (SAOLP) treatment. A comparative analysis was conducted between the two groups, evaluating clinical efficacy, changes in inflammatory markers and immunological parameters, and adverse drug reactions (ADRs). Results: Upon treatment completion, the observation group exhibited an overall response rate (ORR) of 95.00%, whereas the control group showed an ORR of 80.00% (P &lt; 0.05). Additionally, the observation group had a significantly shorter length of hospital stay (LoHS) and a more rapid improvement in symptoms compared to the control group (both P &lt; 0.05). Following treatment, both groups demonstrated significant decreases in interleukin‐2 (IL‐2), interleukin‐4 (IL‐4), interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), and tumor necrosis factor‐α (TNF‐α) levels (all P &lt; 0.05). However, these reductions were more pronounced in the observation group than in the control group (all P &lt; 0.05). Similarly, after treatment, both groups showed significant increases in T cell subsets CD3⁺ and CD4⁺, the CD4⁺/CD8⁺ ratio, and levels of immunoglobulin M (IgM), immunoglobulin A (IgA), and immunoglobulin G (IgG) (all P &lt; 0.05), with these changes being more evident in the observation group than in the control group (all P &lt; 0.05). Both groups experienced adverse reactions during the treatment, with an overall adverse reaction rate (OADRR) of 7.50% in the observation group and 10.00% in the control group (χ² = 0.157, P = 0.692). Conclusions: The combined therapy using SA, BUD, and LEV can significantly improve immune function and reduce inflammatory markers, thereby achieving satisfactory efficacy in treating pediatric BA with a clinically safe profile.

From self-Assembly to healing: Engineering ultra-Small peptides into supramolecular hydrogels for controlled drug release

The aim of this study was the evaluation of suitability of novel mucoadhesive hydrogel platforms for the delivery of therapeutics useful for the management of disorders related to the gastrointestinal tract (GI). At this purpose, here we describe the preparation, the physicochemical characterization and drug delivery behaviour of novel hydrogels, based on self-assembling lipopeptides (MPD02-09), obtained by covalently conjugating lauric acid (LA) to SNA’s peptide derivatives gotten by variously combining D- and L- amino acid residues. LA conjugation was aimed at improving the stability of the precursor peptides, obtaining amphiphilic structures, and triggering the hydrogels formation through the self-assembling. Budesonide (BUD), an anti-inflammatory drug, was selected as model because of its use in the treatment in GI disorders. Preliminary studies were performed to correlate the chemical structure of the conjugates with the key physicochemical properties of the materials for drug delivery. Two lipopeptides, MPD03 and MPD08, were found to form hydrogels (MPD03h and MPD08h, respectively) with characteristics suitable for drug delivery. These materials showed mucoadhesiveness of about 60 %. In vitro studies carried out with BUD loaded hydrogels showed about 70 % drug release within 6 h. Wound healing assessed in Caco-2 and HaCaT cells, showed reduction of cell-free area to values lower than 10 %. Taking together these results MPD03h and MPD08h have been shown to be excellent candidates for BUD delivery.

Integration of mucus and its impact within in vitro setups for inhaled drugs and formulations: Identifying the limits of simple vs. complex methodologies when studying drug dissolution and permeability

Traditionally, developing inhaled drug formulations relied on trial and error, yet recent technological advancements have deepened the understanding of ‘inhalation biopharmaceutics’ i.e. the processes that occur to influence the rate and extent of drug exposure in the lungs. This knowledge has led to the development of new in vitro models that predict the in vivo behavior of drugs, facilitating the enhancement of existing formulation and the development of novel ones. Our prior research examined how simulated lung fluid (SLF) affects the solubility of inhaled drugs. Building on this, we aimed to explore drug dissolution and permeability in lung mucosa models containing mucus. Thus, the permeation of four active pharmaceutical ingredients (APIs), salbutamol sulphate (SS), tiotropium bromide (TioBr), formoterol fumarate (FF) and budesonide (BUD), was assayed in porcine mucus covered Calu-3 cell layers, cultivated at an air liquid interface (ALI) or submerged in a liquid covered (LC) culture system. Further analysis on BUD and FF involved their transport in a mucus-covered PAMPA system. Finally, their dissolution post-aerosolization from Symbicort® was compared using ‘simple’ Transwell and complex DissolvIt® apparatuses, alone or in presence of porcine mucus or polymer-lipid mucus simulant. The presence of porcine mucus impacted both permeability and dissolution of inhaled drugs. For instance, permeability of SS was reduced by a factor of ten in the Calu-3 ALI model while the permeability of BUD was reduced by factor of two in LC and ALI setups. The comparison of dissolution methodologies indicated that drug dissolution performance was highly dependent on the setup, observing decreased release efficiency and higher variability in Transwell system compared to DissolvIt®. Overall, results demonstrate that relatively simple methodologies can be used to discriminate between formulations in early phase drug product development. However, for more advanced stages complex methods are required. Crucially, it was clear that the impact of mucus and selection of its composition in in vitro testing of dissolution and permeability should not be neglected when developing drugs and formulations intended for inhalation.

Methacrylic acid grafted inulin and carboxymethyl cellulose as additives in the development of pH sensitive hydrogel matrix for colon targeting

AbstractCompression‐coated matrix tablets were developed to target budesonide (BUD) in the colonic region using methacrylic acid (MAA) grafted inulin (INU) and carboxymethyl cellulose (CMC). INU was grafted with MAA to impart anionic characteristics to the gum, making it feasible to form a hydrogel by cross‐linking with calcium gluconate (CG). The core matrix made up of MAA‐g‐INU alone disintegrated within 30 min and the core matrix made up of CMC alone completely released BUD within 6 h. The combination of MAA‐g‐INU and CMC produced a rigid matrix, which was able to completely release BUD after 7 h. Compression coating of the core tablets with MAA‐g‐INU and CMC did not release BUD in the first 4 h, and complete BUD release took place in the next 4 h. Compression coating led to the formation of a rigid and viscous gel layer outside the core matrices, which hindered BUD release. We conclude that compression coating with CG cross‐linked CMC and MAA‐g‐INU could be used as a matrix for colonic delivery of drugs.Highlights Compression coated matrices were developed for colonic delivery of BUD. The matrix retained drug release up to 4 h in upper gastrointestinal tract (GIT). The matrix exhibited complete drug release in the next 4 h in the colon.

Budesonide and N-acetylcysteine inhibit activation of the NLRP3 inflammasome by regulating miR-381 to alleviate acute lung injury caused by the pyroptosis-mediated inflammatory response.

The anti-inflammatory effects of budesonide (BUN) and N-acetylcysteine (NAC) attenuate acute lung injury (ALI). The aim of this study was to investigate the effects of combination therapy consisting of BUN and NAC on ALI and the underlying mechanisms. In vitro and in vivo models of ALI were generated by LPS induction. Western blotting was used to detect the expression levels of pyroptosis-related proteins and inflammation-related factors, and RT-qPCR was used to detect the expression of miR-381. Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry, respectively. ELISA was used to detect the levels of inflammation-related factors. HE staining was used to detect lung injury. The results showed that LPS effectively induced pyroptosis in cells and promoted the expression of pyroptosis-related proteins (Caspase1, Gasdermin D and NLRP3) and inflammatory cytokines (TNF-α, IL-6 and IL-1β). The combination of BUN and NAC significantly alleviated LPS-induced pyroptosis and inflammation. In addition, the combination of BUN and NAC effectively promoted miR-381 expression. Transfection of miR-381 mimics effectively alleviated LPS-induced pyroptosis and inflammation, while transfection of miR-381 inhibitors had the opposite effect. miR-381 negatively regulates NLRP3 expression. Treatment with a miR-381 inhibitor or pc-NLRP3 reversed the effects of the combination of BUN and NAC. In a mouse model of ALI, the combination of BUN and NAC effectively improved lung injury, while treatment with a miR-381 inhibitor or pc-NLRP3 effectively reversed this effect. Overall, this study revealed that BUN+NAC inhibits the activation of NLRP3 by regulating miR-381, thereby alleviating ALI caused by pyroptosis-mediated inflammation.

The Role of Nanoparticle Morphology on Enhancing Delivery of Budesonide for Treatment of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease that affects the gastrointestinal tract. The major hurdles impeding IBD treatment are the low targeting efficiency and short retention time of drugs in IBD sites. Nanoparticles with specific shapes have demonstrated the ability to improve mucus retention and cellular uptake. Herein, mesoporous silica nanoparticles (MSNs) with various morphologies were used to deliver budesonide (BUD) for the treatment of IBD. The therapeutic efficacy is strongly dependent on their shapes. The system comprises different shapes of MSNs as carriers for budesonide (BUD), along with Eudragit S100 as the enteric release shell. The encapsulation of Eudragit S100 not only improved the stability of MSNs-BUD in the gastrointestinal tract but also conferred pH-responsive drug release properties. Then, MSNs efficiently deliver BUD to the colon site, and the special shape of MSNs plays a critical role in enhancing their permeability and retention in the mucus layer. Among them, dendritic MSNs (MSND) effectively reduced myeloperoxidase (MPO) activity and levels of inflammatory cytokines in the colon due to long retention time and rapid release in IBD sites, thereby enhancing the therapeutic efficacy against colitis. Given the special shapes of MSNs and pH-responsivity of Eudragit S100, BUD loaded in the voids of MSND (E@MSNs-BUD) could penetrate the mucous layer and be accurately delivered to the colon with minor side effects. This system is expected to complement current treatment strategies for the IBD.

Connecting in situ cone/jet length in electrospinning to fiber diameter and drug release for the rational design of electrospun drug carriers

Towards enabling the rational design of electrospun drug carriers, this study investigated relationships between cone/jet features in electrospinning and operating/solution parameters, fiber diameter or drug release profiles. Cone/jet length were visualized real-time during electrospinning of budesonide (BUD)-loaded poly(caprolactone) (PCL) and poly(D,L-lactide-co-glycolide) (PLGA) solutions. Voltage was varied for BUD-PCL at fixed drug/polymer ratio of 7.4 %, while solution concentration was modulated for BUD-PLGA resulting in drug/polymer ratios of 3.3–4.3 %. In both the BUD-PCL and BUD-PLGA systems, cone length and fiber diameter shared a strong linear relationship (R2 = 0.99, 0.98 respectively). PCL meshes exhibited bi-phasic release profiles, releasing ∼ 95 % BUD over 7 days regardless of fiber diameter, while PLGA meshes exhibited diameter-dependent controlled release. Despite the inconsistent relationship between fiber diameter and release, straight jet length in electrospinning was well-correlated with the Korsmeyer-Peppas parameter for BUD-PCL and the zero-order release parameter for BUD-PLGA (R2 = 0.71, 0.94 respectively). This approach of cone/jet visualization can reduce trial–error experiments and circumvent the cumbersome optimization of several electrospinning parameters for the design of drug-loaded electrospun meshes.

Budesonide Attains Its Wide Clinical Profile by Alternative Kinetics.

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.

Thermodynamic and Structural Study of Budesonide-Exogenous Lung Surfactant System.

The clinical benefits of using exogenous pulmonary surfactant (EPS) as a carrier of budesonide (BUD), a non-halogenated corticosteroid with a broad anti-inflammatory effect, have been established. Using various experimental techniques (differential scanning calorimetry DSC, small- and wide- angle X-ray scattering SAXS/WAXS, small- angle neutron scattering SANS, fluorescence spectroscopy, dynamic light scattering DLS, and zeta potential), we investigated the effect of BUD on the thermodynamics and structure of the clinically used EPS, Curosurf®. We show that BUD facilitates the Curosurf® phase transition from the gel to the fluid state, resulting in a decrease in the temperature of the main phase transition (Tm) and enthalpy (ΔH). The morphology of the Curosurf® dispersion is maintained for BUD < 10 wt% of the Curosurf® mass; BUD slightly increases the repeat distance d of the fluid lamellar phase in multilamellar vesicles (MLVs) resulting from the thickening of the lipid bilayer. The bilayer thickening (~0.23 nm) was derived from SANS data. The presence of ~2 mmol/L of Ca2+ maintains the effect and structure of the MLVs. The changes in the lateral pressure of the Curosurf® bilayer revealed that the intercalated BUD between the acyl chains of the surfactant's lipid molecules resides deeper in the hydrophobic region when its content exceeds ~6 wt%. Our studies support the concept of a combined therapy utilising budesonide-enriched Curosurf®.

Budesonide/Formoterol or Budesonide/Albuterol as Anti-Inflammatory Reliever Therapy for Asthma

Over use of reliever as short acting beta-agonist (SABA) and associated underuse of controller as inhaled corticosteroid (ICS) administered via separate inhalers results in worse asthma outcomes . Such discordance can be obviated by combining both controller and reliever in the same inhaler. So called anti-inflammatory reliever (AIR) therapy comprises the use of a single inhaler containing an ICS such as budesonide (BUD) in conjunction with a reliever as either albuterol (ALB) or formoterol (FORM) ,to be used on demand with variable dosing driven by asthma symptoms in a flexible patient centred regimen. Global guidelines now support the use of BUD-ALB as AIR therapy to reduce exacerbations , either on its own in mild asthma or in conjunction with fixed dose maintenance ICS-long acting beta-agonist (LABA) in moderate to severe asthma . Using BUD-FORM on its own allows patients to seamlessly move in an intuitive flexible fashion between AIR or maintenance and reliever therapy (MART) , by stepping up and down the dosing escalator across a spectrum of asthma severities . Head to head clinical studies are indicated to compare BUD-FORM versus BUD-ALB as AIR in mild asthma ,and also BUD-FORM as MART versus BUD-ALB as AIR plus maintenance ICS-LABA in moderate to severe asthma. Patients should be encouraged to make an informed decision in conjunction with their health care professional regarding the best therapeutic option tailored to their individual needs , which in turn is likely to result in long term compliance and associated optimal asthma control.

Atomized inhalation of Icaritin reduces airway inflammation and remodeling in asthmatic mice

Background Asthma is a disease characterized by airway hyperresponsiveness and airway inflammation. Icaritin (ICT) is a plant hormone with various pharmacological activities such as anti-inflammatory, immune regulation, and anti-tumor. This study mainly explored the effects of nebulized inhalation of ICT on airway inflammation and airway remodeling in asthmatic mice. Method Different groups of ovalbumin (OVA)-induced asthma mice with acute and chronic airway inflammation received ICT. Asthmatic mice received budesonide (BDND) aerosol inhalation as a positive control, while normal control and asthma model mice received the same volume of saline. Following finishing of the study, analyses were conducted on behavioral tests, biochemical indices, and histological structures of lung tissues. Results Aerosol inhalation of ICT can notably reduce inflammatory cells infiltration around the airways and pulmonary vessels, and suppressed goblet cell hyperplasia in asthmatic mice. Long-term inhalation of ICT can decrease airway collagen deposition and airway smooth muscle hyperplasia, and alleviate airway hyperresponsiveness, mirroring the effects observed with hormone employed in clinical practice. Conclusion Nebulized inhalation of ICT can effectively inhibit airway inflammation in asthmatic mice, improve airway remodeling, and reduce airway hyperresponsiveness, with effects similar to those of hormones. It may serve as a potential candidate used as a hormone replacement asthma treatment.

Assessment of Critical Quality Attributes of Budesonide and Formoterol Fumarate Dihydrate in Dry Powder Inhalers Marketed in Pakistan

Dry powder inhalers (DPIs) have been well established and recognized for the delivery to the lungs. It provides better drug stability, less irritable, easy to use with deep penetration of drugs in the lungs. Budesonide (BDS) and formoterol fumarate dihydrate (FFD) indicated in pulmonary diseases. The main aim of the study is to evaluate BDS, FFD and their marketed DPIs product in Pakistan were compare in quality and performance with the reference product. The particle size distribution and aerodynamic characterization were analyzed by laser diffraction and multi stage liquid impinger, respectively. The particle density and delivered dose uniformity were also determined. HPLC was also used for the qualitative and quantitative estimation of BDS and FFD along with its marketed products. Laser diffraction particle size analyzer revealed Dv50 53.27 to 56.34 and#181;m having surface area 1815 to 2304 cm3/g. The percentages of emitted dose (%ED) and fine particle fraction (%FPF) was found 98.19 to 99.23% and 31.57 to 34.87%, respectively. The mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) were calculated 2.62 to 2.89 and#181;m and 1.99 to 2.54, correspondingly. The quantitative assay of BDS and FFD in all the commercial DPIs and reference product were well within the pharmacopeial limit i.e. 97.26 to 101.36%. The average of ten units results of delivered dose uniformity for BSD and FFD were also found in the range i.e. 97.97 to 103.19% and 98.48 to 104.41 %, respectively. The results of evaluation of parameters of DPIs like Dv50, %ED, %FPF, MMAD, GSD has shown compliance with the pharmacopeial standards. It is concluded that the all DPIs of BDS/FFD marketed in Pakistan has revealed conformance with the standard of pharmacopoeia and meet the requirements of drug regulatory authority of Pakistan.

Evaluating the affordability of asthma, chronic obstructive pulmonary disease, and cystic fibrosis medicines in a middle-income country

BackgroundA heavy financial burden is imposed on patients suffering from chronic diseases due to medicine out-of-pocket payments.ObjectivesThis study focuses on assessing the affordability of medications used for chronic respiratory diseases (CRDs) such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) in Iran, specifically on the category R medicines listed in the 2017 Iran drug list (IDL) that are used for the treatment of these diseases, based on the anatomical therapeutic chemical (ATC) drug code.MethodsThe affordability of medicines in mono and combination therapy approaches was assessed in CRDs using the World Health Organization/Health Action International (WHO/HAI) methodology. Accordingly, if out-of-pocket payment for 30-days of pharmacotherapy exceeds one day for the lowest-paid unskilled government worker (LPGW), it’s considered non-affordable.ResultsBased on the monotherapy approach, our finding demonstrates that all generic medicines of category R were affordable. However, branded drugs such as Symbicort®, Pulmicort Respules®, Flusalmex®, Seretide®, Fluticort Plus®, Seroflo®, and Salmeflo® cost between 1.2 and 2.5 days’ wage of LPGW and considered unaffordable despite 70% insurance coverage. Moreover, based on the affordability ratio in the combination therapy approach, all medicines used in asthma, COPD, and CF patients with mild respiratory problems are affordable except omalizumab (inj), which is non-affordable due to its high price and no insurance coverage.ConclusionResults showed that the existing insurance coverage does not protect households from hardship, so more considerations are needed such as different insurance schedules and patient support programs.