Dry Powder and Budesonide Inhalation Suspension Deposition Rates in Asthmatic Airway-Obstruction Regions

Abstract

Steroid inhalation is the standard bronchial asthma therapy and it includes powdered metered doses, dry powder, and nebulizer suspension. However, particle sizes vary widely. The research goal was to demonstrate that different budesonide administration forms and devices have various deposition rates in the airway obstruction region. Here, we compared relative inhalation therapy efficacies and identified therapies that delivered the highest drug doses to the airway obstruction region. Weibel's anatomy data were used to identify the airway obstruction region in asthma. Based on European Standardization Committee data, we investigated the diameters of the drug particles being deposited there and evaluated the average particle size and distribution of the budesonide dosage forms and application devices. Drug dose depositions were measured by HPLC at each stage of a Cascade Impactor. Weibel's anatomy data indicated that the 1st–4th bronchial generations comprised the airway obstruction region and corresponded to the tracheobronchial area. According to the European Standardization, particles 2–6 µm in diameter were readily deposited there. The proportions of particles in this size range were 33.0%, 32.0%, 59.0%, and 78.0% for Turbuhaler, Symbicort, mesh-type NE-U22 suspension, and jet-type NE-C28 suspension, respectively. We localized the airway obstruction regions of bronchial asthma and identified the optimal inhalation therapy particle size. An electric nebulizer was more efficacious for budesonide administration than dry powder delivery. The NE-C28 treatment deposited 2.36x more budesonide in the airway obstruction region than dry powder delivery systems.

Development of nintedanib nanosuspension for inhaled treatment of experimental silicosis

“…To this end, we have focused on enhancing the lung pharmacokinetics by endowing our formulation with the ability to avoid natural clearance mechanisms inevitably encountered following the settlement on lung lumen. Multiple reports have demonstrated that nebulization provides markedly greater or more uniform deposition in human lungs compared to dry powder inhalation 52,53 . We here show that NTB‐NS can be aerosolized with a vibrating mesh nebulizer without perturbing the physicochemical properties that enable enhanced lung pharmacokinetics.…”

“…Multiple reports have demonstrated that nebulization provides markedly greater or more uniform deposition in human lungs compared to dry powder inhalation. 52,53 We here show that NTB-NS can be aerosolized with a vibrating mesh nebulizer without perturbing the physicochemical properties that enable enhanced lung pharmacokinetics. Of note, vibrating mesh nebulizers have been shown in clinical studies to provide superior lung deposition or therapeutic outcomes compared to jet nebulizers which have a longer history of clinical use.…”

Continuous flow process for preparing budesonide

“…2 ) [ 23 ]. From the formulation point of view, estimation of budesonide particle size expands its usage in multiple dosage forms especially aerosol or nebulizer [ 24 – 26 ]. Also, particle size distribution in the dosage forms (suspension or aerosol) is typically associated with absorption rate and bioavailability.…”

Development of an Innovative, Carrier-Based Dry Powder Inhalation Formulation Containing Spray-Dried Meloxicam Potassium to Improve the In Vitro and In Silico Aerodynamic Properties

“…From the percentage value for 3 µm ( Figure A1, blue line) we can get the mass of the particles with a diameter less than 3 µm, from which we get FPF < 3 µm as a percentage of the ED. This value has also been expressed by several publications recently [77,78], because in the sub-tracheal region of the lung-in the deep lung-mainly particles below 3 µm form deposits [79]; thus, when comparing the aerodynamic properties of the DPI formulations, the calculation of the deep lung deposit value is also expedient. It should be noted that in addition to the reported results, the FPF < 4.7 µm calculation is always performed as a control, which is exemplified in the literature [80].…”