Development of an Inhaled Dry-Powder Formulation of Tobramycin Using PulmoSphere™ Technology

Abstract

At present, the only approved inhaled antipseudomonal antibiotics for chronic pulmonary infections in patients with cystic fibrosis (CF) are nebulized solutions. However, prolonged administration and cleaning times, high administration frequency, and cumbersome delivery technologies with nebulizers add to the high treatment burden in this patient population. PulmoSphere™ technology is an emulsion-based spray-drying process that enables the production of light porous particle, dry-powder formulations, which exhibit improved flow and dispersion from passive dry powder inhalers. This review explores the fundamental characteristics of PulmoSphere technology, focusing on the development of a dry powder formulation of tobramycin for the treatment of chronic pulmonary Pseudomonas aeruginosa (Pa) infection in CF patients. This dry powder formulation provides substantially improved intrapulmonary deposition efficiency, faster delivery, and more convenient administration over nebulized formulations. The availability of more efficient and convenient treatment options may improve treatment compliance, and thereby therapeutic outcomes in CF.

Advancements in Dry Powder Inhaler

“…The drug is dissolved in a solvent and then precipitated to produce fine particles [25,26]. This technique allows for greater control of particle properties like morphology, porosity, density, particle size and distribution, which further govern powder properties such as powder flow and dispersibility [27].…”

“…Dispersible powders with improved aerodynamic properties have been achieved without the addition of carrier particles; the powder properties are improved. High drug loadings about 90-95% w/w are possible [25]. Improvements in lung delivery can be achieved by spray dried, low density and highly porous particles which decrease interparticle cohesive forces [27].…”

“…The PulmoSpheres delivery is independent of the patient's inspiratory flow rate, reducing dosing variability. TOBI Podhaler which utilizes PulmoSphere technology is indicated for the management of cystic fibrosis patients with Pseudomonas aeruginosa [25].…”

Tobramycin Inhalation Powder in Cystic Fibrosis Patients: Response by Age Group

“…13 TIP delivers light, porous, engineered particles via the portable T-326 dry powder inhaler. 14 The inhaler has low air flow resistance, which allows the patient to generate a high inspiratory flow and achieve reliable dose delivery. In studies in both healthy volunteers and patients with CF, TIP had a similar pharmacokinetic profile to TIS, but resulted in a more efficient and rapid delivery of tobramycin to the lungs.…”

“…In studies in both healthy volunteers and patients with CF, TIP had a similar pharmacokinetic profile to TIS, but resulted in a more efficient and rapid delivery of tobramycin to the lungs. [14][15][16] However, effective use of dry powder inhalers among patients with chronic respiratory diseases can be affected by factors such as age and disease severity. 17,18 Therefore, it is important to confirm that the observed pharmacokinetic profile of TIP translates into favorable clinical outcomes, particularly in patients with lower inspiratory effort, such as young children and patients with more severe disease.…”