Budesonide Powder Research Articles

Efficacy of Fluticasone and Salmeterol Dry Powder in Treating Patients with Bronchial Asthma and Its Effect on Inflammatory Factors and Pulmonary Function.

Objective To evaluate the efficacy of fluticasone and salmeterol dry powder in treating patients with bronchial asthma and its effects on inflammatory factors and pulmonary function. Methods One hundred patients with bronchial asthma, admitted to our hospital between April 2019 and June 2020, were enrolled and assigned into two groups using the random number table method. The observation group (n = 50) received budesonide powder, and the experimental group received fluticasone and salmeterol dry powder. The two groups were compared with regard to clinical efficacy, inflammatory factors, pulmonary function, and adverse reactions. Results In the experimental group, the total effective rate of treatment was significantly higher than that in the observation group (P < 0.05); after treatment, the levels of inflammatory factors in the experimental group were lower than those in the observation group (P < 0.05); after treatment, lung function in the experimental group was significantly higher than that in the observation group (P < 0.05); the incidence of adverse reactions in the experimental group was significantly lower than that in the observation group (P < 0.05). Conclusion Salmeterol and fluticasone powder has shown impressive clinical benefits in the treatment of bronchial asthma patients. It might be a viable approach to reduce inflammatory factors and improve pulmonary function. Moreover, its good clinical safety profile makes it a promising treatment that ought to be promoted and used widely.

Effect of Inhalation of Low-Dose Budesonide Powder Combined with Pulmonary Rehabilitation in the Treatment of Bronchial Asthma

Effect of Inhalation of Low-Dose Budesonide Powder Combined with Pulmonary Rehabilitation in the Treatment of Bronchial Asthma

Improved respirable fraction of budesonide powder for dry powder inhaler formulations produced by advanced supercritical CO2 processing and use of a novel additive

A budesonide (BDS) suspension was obtained via advanced supercritical carbon dioxide (scCO2) processing. Thereafter, the suspension was freeze-dried (FD) to produce BDS particles for dry powder inhaler formulations (scCO2/FD processing). The scCO2/FD processed BDS powder showed low crystallinity by powder X-ray diffraction and a rough surface by scanning electron microscopy. The respirable fraction of BDS was assessed using a twin impinger and revealed that the amount of the scCO2/FD processed sample that reached stage 2 was 4-fold higher than that of the supplied powder. To extend the utility of scCO2 processing, BDS particles for dry powder inhalers were fabricated by combining the scCO2 system with various additives. When BDS was processed via scCO2/FD in the presence of the novel additive, namely, monoglyceride stearate (MGS), the residual BDS/MGS particles remaining in the capsule and devices decreased, followed by an increase in the respirable fraction of BDS 6-fold higher than with the supplied powder. The scCO2/FD processed BDS/MGS particles had a smooth surface, in contrast to the scCO2/FD processed BDS particles. A combination of BDS and an appropriate additive in scCO2 treatment may induce changes in particle surface morphology, leading to an improvement in the inhalation properties of BDS.

Engineered Dry Powder Budesonide Particles for Improved Pediatric Inhalation Therapy

Corticosteroids have been the cornerstone treatment for asthma; however, several challenges exist with current inhaled steroids for pediatric patients. Dry powder corticosteroids are now being prescribed to pediatric patients 蠅 6 years of age with some success; however, many younger patients lack the inhalation energy required to properly fluidize and deagglomerate the drug particles, which leads to improper drug delivery, increases oral steroid exposure, and reduces long term compliance. We tested the hypothesis that engineered budesonide NanoClusters, drug particles with decreased density per surface area, would improve fluidization and deagglomeration efficiency compared to commercially available micronized budesonide and Pulmicort™ powders at flow rates seen in pediatric patients. Micronized budesonide powder was wet milled into micron sized NanoClusters using a Netzsch MiniCer Media Mill and then lyophilized. Budesonide powders were tested at various flow rates in a custom fabricated electronically controlled flow rate adjustable pneumatic device coupled to an Anderson Cascade Impactor. NanoCluster budesonide achieved EFmax (~85%) at a flow rate of 2.5 L/minute, whereas EF of micronized budesonide and Pulmicort™ were only minimally emitted (~2‐3%) at this flow rate. Importantly, fine particle fraction (FPF) of NanoClusters was significantly elevated compared to micronized budesonide and Pulmicort™ formulations. The data suggests that NanoCluster formulation improves budesonide dispersion properties at low flow rates, potentially allowing a lower unit dose formulation of budesonide for children without altering the effective therapeutic dose; increasing overall therapeutic index.

Development of Budesonide Nanocluster Dry Powder Aerosols: Formulation and Stability

The physical and chemical stability of dry powder aerosol formulations is an essential component in the development of an inhaled therapeutic. The pharmaceutical processing methods and storage conditions are primary determinants of the stability of a dry powder inhaler (DPI) formulation. Wet milling was used to produce budesonide NanoClusters (NCs), which are agglomerates of drug nanoparticles (≈ 300 nm) with a mean aerodynamic diameter between 1 and 3 µm, capable of deep lung penetration. In this study, the reproducibility of NC processing and performance was established. The physical stability of a selected budesonide NC formulation was investigated using industry standard dose content uniformity and cascade impaction techniques. The chemical stability of the lead formulation was also determined as a function of processing parameters and storage conditions. This study confirms the reproducibility and robust stability of NC powders as a novel means to turn drug particles into high-performance aerosols.

Influence of lactose carrier particle size on the aerosol performance of budesonide from a dry powder inhaler

The purpose of this study was to evaluate the effect of carrier particle size on properties of dry powder and its effect on dry powder inhaler (DPI) performance. Commercial α-lactose-monohydrate, a commonly used carrier in DPI formulations, was carefully sieved to obtain different lactose size fractions, namely Lac A (90–125μm), Lac B (63–90μm), Lac C (45–63μm), Lac D (20–45μm), and Lac E (<20μm). The lactose samples were analysed in terms of size, shape, solid state, density, and flowability. Lactose particles were blended with budesonide (<5μm) powder to generate five different formulations. These formulations were then evaluated in terms of budesonide–lactose adhesion properties, drug content homogeneity, and in vitro aerosolisation performance. The results demonstrated that lactose samples with smaller particle volume mean diameter have higher amorphous lactose content, higher true density (linear, r2=0.9932), higher surface smoothness (linear, r2=0.8752), smaller angularity (linear, r2=0.921), smaller bulk density, higher porosity (linear, r2=0.914), poorer flowability, and higher specific surface area. In general, the smaller the lactose particles the smaller are the budesonide–lactose adhesion properties. Budesonide formulated with smaller lactose particles exhibited smaller aerodynamic diameter and higher amounts of budesonide were delivered to lower stages of the impactor indicating improved DPI aerosolisation performance. However, the use of lactose particles with smaller volume mean diameter had a detrimental effect on budesonide content homogeneity and caused an increase in the amounts of budesonide deposited on oropharyngeal region. Therefore, particle size of the lactose within dry powder inhaler formulations should be selected carefully. Accordingly, higher drug aerosolisation efficiency of lactose particles with smaller size may have to be balanced due to considerations of other disadvantages including poorer flowability, reduced formulation stability, higher potential side effects, and higher dose variability.

Does the United States Pharmacopeia Throat Introduce De-agglomeration of Carrier-Free Powder from Inhalers?

We hypothesize that the USP induction port may de-agglomerate carrier-free powder emitting from dry powder inhalers (DPIs). Aerosols emitting from a range of DPIs (Spinhaler®, Turbuhaler® and Osmohaler™) and induction ports (USP throat, straight tube, Alberta idealized mouth-throat geometry (AG)) were sized by laser diffraction. Total drug recovery was obtained by HPLC and fine particle fraction computed. Air flow patterns were simulated using Computational Fluid Dynamics (CFD). The straight tube did not de-agglomerate emitted powder. However, the USP throat and AG further de-agglomerated powders from the Spinhaler, but not the Turbuhaler and Osmohaler. While budesonide powder deposited similarly in all induction ports, deposition was significantly higher in the AG for both DSCG and mannitol. CFD revealed agglomerates impacting on the USP throat with higher localized velocity compared with the straight tube. CFD further showed a more complex flow pattern with high-velocity air jets in the AG, which explains the higher FPF for DSCG and the lower FPF for mannitol using the AG. The USP throat further de-agglomerated the emitted powder from the DPI when it did not sufficiently disperse the powder. Other tools such as laser diffraction may be used for cross-examining to avoid artifacts in the results.

Budesonide Microemulsions for Enhancing Solubility and Dissolution Rate

Budesonide belongs to Class II in the Biopharmaceutics Classification System (BCS) for its high permeability and poor aqueous solubility. The purpose of this study was to improve the solubility and dissolution rate of budesonide using an o/w microemulsion system in order to develop a nasal formulation. Based on the results of the solubility study and pseudo ternary phase diagrams, microemulsions of about 80 nm in mean diameter were formulated using isopropyl myristate and Labrasol as an oil phase and a surfactant, respectively. Solubility of budesonide in the microemulsions increased up to 6.50 mg/mL, which is high enough for a nasal formulation. In vitro release profiles of budesonide significantly increased from the microemulsions compared to that of the budesonide powder. These results suggest that the microemulsions of budesonide could further be developed into a clinically useful nasal formulation.

Evaluation of supercritical fluid engineered budesonide powder for respiratory delivery using nebulisers

Abstract Objectives Currently, suspensions prepared from micronised drug substances are the only delivery system marketed for nebulisation of steroids, and reported inconsistent or low bioavailability arising from their use provides a rationale for researching alternative formulations. Supercritical fluid processing of drug substances to obtain respirable-sized particles has been used over the last decade to formulate dry powder inhalers. We aimed thus to process budesonide powder to improve its deposition characteristics. Methods In an attempt to overcome the limitations of nebuliser suspensions when prepared from micronised drug particles, budesonide powder was processed using a supercritical fluid based process and suspended using Tween 80 as a surfactant to provide an aqueous nebuliser formulation. The in-vitro characteristics of the emitted dose on nebulisation for the prepared suspension were then compared to a commercially available suspension formulation of budesonide using a jet and a vibrating mesh nebuliser. Key findings The results showed a significant improvement of the in-vitro deposition properties of the suspension containing supercritical fluid engineered budesonide particles. Conclusions The results indicated the benefit of such materials compared with traditionally micronised drug powders.

Evaluation of supercritical fluid engineered budesonide powder for respiratory delivery using nebulisers

Currently, suspensions prepared from micronised drug substances are the only delivery system marketed for nebulisation of steroids, and reported inconsistent or low bioavailability arising from their use provides a rationale for researching alternative formulations. Supercritical fluid processing of drug substances to obtain respirable-sized particles has been used over the last decade to formulate dry powder inhalers. We aimed thus to process budesonide powder to improve its deposition characteristics. In an attempt to overcome the limitations of nebuliser suspensions when prepared from micronised drug particles, budesonide powder was processed using a supercritical fluid based process and suspended using Tween 80 as a surfactant to provide an aqueous nebuliser formulation. The in-vitro characteristics of the emitted dose on nebulisation for the prepared suspension were then compared to a commercially available suspension formulation of budesonide using a jet and a vibrating mesh nebuliser. The results showed a significant improvement of the in-vitro deposition properties of the suspension containing supercritical fluid engineered budesonide particles. The results indicated the benefit of such materials compared with traditionally micronised drug powders.

Influence of process parameters in the ASES process on particle properties of budesonide for pulmonary delivery

Budesonide was micronized by precipitation in supercritical carbon dioxide by using the aerosol solvent extraction system at various process conditions. The process is characterised by spraying an organic solution of budesonide into the supercritical fluid (SCF), precipitation of the drug in the SCF and extraction and recovery of the solvent. The micronized budesonide particles were characterized physico-chemically for their morphology, crystallinity, size distribution and for their aerodynamic behaviour. The particle size distribution of the powder products was similar, regardless of the process conditions used for the crystallization. Also, the morphology of the particles did not differ between the batches. However, the aerodynamic properties of the precipitated batches were significantly different between the batches produced and as compared to a jet-milled budesonide powder. In conclusion, the process conditions in the SCF precipitation may influence the aerodynamic properties, although other physico-chemical parameters appear to be similar.

Stability and aerodynamic behaviour of glucocorticoid particles prepared by a supercritical fluids process

Particle processing techniques using supercritical fluids (SF) are potential alternative technologies to design particles for inhalation. Powders of budesonide and flunisolide were prepared using solution enhanced dispersion by supercritical fluids (SEDS) process. The aim was to determine thermodynamic stability of different polymorphs of flunisolide including new forms from SEDS technology and to characterise micronised and SEDS produced powders of budesonide and flunisolide for their suitability as inhalation powders. Acetone and methanol solutions of budesonide and flunisolide, with a concentration of 2.5 mg/ml, were used for the particle preparation. The pressure was 100 bar and temperatures were 60 degrees C or 80 degrees C. The flow rates of CO(2) and drug solution were 9 ml/min and 0.3 ml/min, respectively. Chemical purity of different polymorphs of flunisolide was estimated using high performance liquid chromatography (HPLC) and thermal behaviour was determined using differential scanning calorimetry (DSC). Particle morphology and surface examination were performed using scanning electron microscopy (SEM) and atomic force microscopy (AFM), respectively. The particle size distribution and density of the powders were determined with the help of Coulter Counter and helium pycnometer respectively. The in vitro deposition of the powders was studied using multistage liquid impinger (MLI). From the stability study, it was found that the two forms of flunisolide, polymorphs II and hemihydrate, were the most stable. Flunisolide form III was transformed to hemihydrate during the stability study. The chemical purity of the material was increased after SEDS processing. SEDS produced powders of budesonide and flunisolide form III from acetone showed narrow volumetric particle size distributions with 90% of the particles below 4 microm and geometric mean size around 3 microm. However, in the MLI study, budesonide powder obtained from SEDS with acetone showed favorable deposition in the lower stages with a mass median aerodynamic diameter (MMAD) of around 3 microm whilst the flunisolide form III was preferentially deposited in the higher stages of the MLI with MMAD of over 5 microm, due to aggregation of the particles. Particles of budesonide and flunisolide, in the size range, suitable for inhalation, were reproducibly produced using SEDS.

Comparison of two budesonide powder inhalers, Easyhaler® and Turbuhaler®, in steroid-naı̈ve asthmatic patients

The objective of this multicenter study was to compare the clinical efficacy, safety, and acceptability of Easyhaler® and Turbuhaler® for the delivery of budesonide 200 μg/dose twice daily in steroid-naı̈ve asthmatic patients. Three hundred and twenty-six newly diagnosed, steroid-naı̈ve adult patients with mild-to-moderate asthma were recruited into this randomized, double-blind, double-dummy, parallel-group study, comprising a 2-week run-in period and 8 weeks of treatment. Patients received budesonide inhalation powder 400 μg/day either via Easyhaler® (n = 159) or via Turbuhaler® (n = 167), plus salbutamol inhalation powder (100 μg/dose) via Easyhaler® as rescue therapy. The study was completed by 292 patients: 143 in the Easyhaler® group and 149 in the Turbuhaler® group. The primary outcome variable, mean morning peak expiratory flow (PEF), improved significantly and almost similarly by 36.3 and 30.6 l/min, respectively, from run-in to weeks 7–8. At weeks 7–8, the mean (SE) difference in morning PEF between the two treatments was 7.1 (9.4) l/min (90% CI from −8.4 to 22.6) on per protocol analysis, which was within the defined limits for therapeutic equivalence. There were no significant differences between treatments in terms of secondary efficacy variables or adverse events. However, patients found Easyhaler® more acceptable than Turbuhaler®. The results show that budesonide via Easyhaler® is clinically as effective as Pulmicort® Turbuhaler® when equal daily doses of budesonide are delivered to steroid-naı̈ve asthmatic patients. Moreover, patients found Easyhaler® more acceptable than Turbuhaler®, and a majority would prefer Easyhaler® if given a choice.

Efficacy of topical corticosteroid powder for nasal polyps: a double-blind, placebo-controlled study of budesonide

Budesonide has been used for a number of years as a topical nasal corticosteroid in the treatment of nasal allergy and nasal polyps. Recently, a new device for powder insufflation where no constituents or preservatives are included has been developed (Rhinocort Turbuhaler, Astra Draco AB, Sweden). The present investigation was designed in order to study the efficacy of topical budesonide powder as the only treatment of nasal polyps. A total of 126 patients entered the study. The medical history and clinical recordings included symptoms and signs, a semiquantitative test of smell and measurement of nasal expiratory peak flow index. Medication was either 200 or 400 micrograms of budesonide powder b.i.d. or placebo. After 1 month an overall assessment of treatment efficacy was made to determine whether the treatment had been a success or a failure. The results showed a statistically significant improvement of symptoms and signs in the actively treated groups. The increase in expiratory peak flow index was about 60% in the actively treated groups as opposed to 16% in the placebo group. The overall assessment of treatment efficacy showed success in about 82% of actively treated patients as opposed to about 43% in the placebo group. It is concluded that budesonide powder is useful in the treatment of nasal polyps.

Powder administration of pure budesonide for the treatment of seasonal allergic rhinitis

The objective of this study was to compare the efficacy and safety of a pure powder formulation of budesonide, delivered from a new multi-dose dispenser for nasal drug application, with the commercially available budesonide pressurized aerosol, and with placebo. Of 116 patients with grass pollen-induced allergic rhinitis, 112 finished the study, which comprised a 4-week treatment period, preceded by a 1-week run-in period. The patients were randomized to four parallel treatment groups: budesonide powder 400 micrograms daily; budesonide powder 800 micrograms daily; budesonide aerosol 400 micrograms daily; and placebo powder. Treatment was given once daily in the morning. The study was double-blind regarding comparison between budesonide powder and placebo. Assessment of efficacy, made by comparing mean scores of nasal symptoms and use of rescue medication, showed equal efficacy of all three budesonide groups compared with placebo. There were no differences between budesonide-and placebo-treated groups with regard to side effects. Budesonide treatment had no demonstrable effect on the HPA-axis assessed by measurement of 24-h urine cortisol. We conclude that budesonide, delivered as pure powder from a multi-dose dispenser, is effective and safe for the treatment of seasonal allergic rhinitis. This new formulation is a good alternative to the commercially available preparations, as it does not contain carrier gas, preservatives or lubricants.

54 Mass provocation for entry into a study establishing efficacy and tolerability of budesonide powder (turbohaler) in children with seasonal allergic rhinitis

54 Mass provocation for entry into a study establishing efficacy and tolerability of budesonide powder (turbohaler) in children with seasonal allergic rhinitis

59 Pure budesonide powder for the treatment of seasonal allergic rhinitis

59 Pure budesonide powder for the treatment of seasonal allergic rhinitis