Budesonide Research Articles

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.

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

ABSTRACT Asthma and Chronic Obstructive Pulmonary Disease (COPD) are major global health issues, with inhalation therapy being a primary treatment method. However, dry powder inhalers (DPIs) often face the issue of drug particle aggregation, which can reduce drug delivery efficiency. This study aims to investigate particle aggregation and optimize the cohesion–adhesion balance to improve inhalation efficiency. Advanced techniques such as atomic force microscopy and Raman imaging were employed to analyze particle interactions and aggregation behavior, focusing on lactose ratios, particle shapes, and drug-drug interactions. The therapeutic efficacy of optimized formulations containing Budesonide (BUD) and Arformoterol (AFT) was evaluated in an asthma model. Specifically, sRAW, neutrophil count, and tidal volume values were significantly improved compared to the positive control group, with p-values below 0.01. AFT demonstrated equivalent efficacy to Formoterol at half the dose. Additionally, pharmacokinetic (PK) studies showed that both drugs exhibited similar in vivo behavior, confirming the therapeutic superiority of AFT. (p-value for AUC0-t and Cmax: 0.646 and 0.153, respectively) The key findings highlight that formulation optimization significantly reduces particle aggregation and improves drug delivery efficiency in DPI (FPF for AFT and BUD: 39.4% and 50.6%, respectively), suggesting the potential for enhanced clinical outcomes in asthma and COPD patients. This study provides valuable insights for the formulation development of inhalable therapies.

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 < 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 < 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 < 0.05). However, these reductions were more pronounced in the observation group than in the control group (all P < 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 < 0.05), with these changes being more evident in the observation group than in the control group (all P < 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.

Meta-analysis of the efficacy of budesonide and ambroxol hydrochloride inhalation in children with pneumonia and their effects on inflammatory response

Childhood pneumonia, often caused by acute upper respiratory tract infections or bronchitis, is one of the leading causes of mortality in children. Nebulized inhalation, as a low-risk treatment method, has garnered significant attention. However, its effectiveness and safety remain controversial. In this study, a systematic review of relevant literature on the use of budesonide (BUD) and ambroxol hydrochloride (AMB) inhalation in the treatment of childhood pneumonia was conducted, and a total of 10 articles were included. The meta-analysis revealed an odds ratio (OR) of 1.61 and an I2 value of 0.00 % for the effectiveness of combined BUD and AMB inhalation therapy in children with pneumonia, indicating no heterogeneity among the studies in terms of effectiveness. The OR values for BUD or AMB inhalation in alleviating cough, lung auscultation abnormalities, respiratory distress, body temperature, and cyanosis of the lips in children with pneumonia all favored the combined BUD therapy, showing significant relief of the aforementioned symptoms. However, due to variations in drug dosage and administration methods, high heterogeneity was observed. This study suggested that combined BUD and AMB inhalation therapy has better efficacy in treating childhood pneumonia, and BUD combined with AMB inhalation is more effective in alleviating symptoms such as cough, lung auscultation abnormalities, respiratory distress, normalizing body temperature, and reducing cyanosis of the lips. Nevertheless, further validation is required due to the limited sample size and substantial heterogeneity in the included studies. To sum up, this study provides the first analysis of the efficacy and inflammatory response of BUD and AMB inhalation in children with pneumonia. Future research should aim to verify and clarify these findings, considering the limitations of the existing studies in terms of sample size and heterogeneity.

Preparation and evaluation of βcyclodextrin-based nanosponges loaded with Budesonide for pulmonary delivery

Budesonide (BUD) is a glucocorticosteroid used to treat chronic obstructive pulmonary disease. Despite this, it is a hydrophobic compound with low bioavailability. To address these hurdles, non-toxic and biocompatible βcyclodextrin-based nanosponges (βCD-NS) were attempted. BUD was loaded on five different βCD-NS at four different ratios. NS with 1,1′-carbonyldiimidazole (CDI) as a crosslinking agent, presented a higher encapsulation efficiency ( ̴ 80%) of BUD at 1:3 BUD: βCD-NS ratio (BUD-βCD-NS). The optimized formulations were characterized by Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), water absorption capacity (WAC), scanning electron microscopy (SEM), X-ray powder diffraction studies (XRD), particle size, zeta potential, encapsulation efficiency, in vitro and in vivo release studies, acute toxicity study, solid-state characterization, and aerosol performance. In vitro-in vivo correlation and cytotoxicity of the formulations on alveolar cells in vitro were further determined. In vitro and in vivo studies showed almost complete drug release and drug absorption from the lungs in the initial 2 h for pure BUD, which were sustained up to 12 h from BUD loaded into nanosponges (BUD-βCD-NS). Acute toxicity studies and in vitro cytotoxicity studies on alveolar cells proved the safety of BUD-βCD-NS. Several parameters, including particle size, median mass aerodynamic diameter, % fine particle fraction, and % emitted dose, were evaluated for aerosol performance, suggesting the capability of BUD-βCD-NS to formulate as a dry powder inhaler (DPI) with a suitable diluent. To sum up, this research will offer new insights into the future advancement of βCD-NS as drug delivery systems for providing controlled release of therapeutic agents against pulmonary disease.

Effect of Montelukast Combined with Budesonide on Inflammatory Response and Pulmonary Function in Children with Cough Variant Asthma: A Meta-analysis.

This meta-analysis aimed to compare the efficacy of montelukast (MKST) combined with budesonide (BUD) and BUD alone in the treatment of pulmonary inflammation and pulmonary function in children with cough variant asthma (CVA). Five electronic databases were searched for studies about MKST+BUD therapy and BUD alone therapy on inflammation and pulmonary function in CVA children from inception to November 23, 2021. Twenty-two articles were included. The results showed that, compared with BUD alone, the combination treatment could achieve better improvement of pulmonary function and lower levels of inflammation (MKST+BUD group: FEV1: SMD = 2.77, 95% CI: 2.07, 3.46; FVC: SMD = 2.54, 95% CI: 1.82, 3.27; PEF: SMD = 2.27, 95% CI: 1.79, 2.75; IgE: SMD = -7.95, 95% CI: -9.66, -6.25; TNF-α: SMD = -4.67, 95% CI: -6.04, -3.31; IL-8: SMD = -8.18, 95% CI: -11.46, -4.90; BUD alone group: FEV1: SMD = 1.83, 95% CI: 1.34, 2.31; FVC: SMD = 1.39, 95% CI: 0.93, 1.84; PEF: SMD = 1.51, 95% CI: 1.13, 1.89; IgE: SMD = -4.93, 95% CI: -6.14, -3.72; TNF-α: SMD = -2.78, 95% CI: -3.76, -1.80; IL-8: SMD = -4.94, 95% CI: -7.10, -2.79). To conclude, compared with BUD alone, MKST+BUD therapy was found to be more effective in improving pulmonary function and reducing inflammation in CVA children. Key Words: Montelukast, Budesonide, Cough variant asthma, Children, Pulmonary function, Inflammatory markers, Meta-analysis.