Polymeric controlled release inhalable powder produced by vibrational spray-drying: One-step preparation and in vitro lung deposition

摘要

Innovative polymeric controlled release inhalable dry powders containing dexamethasone were developed for the treatment of pulmonary diseases. Powders were prepared in one step by vibrational atomization spray-drying using an organic solution containing dexamethasone, poly(e-caprolactone) and a surfactant. The characteristics of the powders were monitored considering the drug content, morphological features, mean particle size, drug-polymer-surfactant compatibility and physical state. In vitro dexamethasone release was studied applying the dialysis bag method. The dose uniformity of the powders, their aerodynamic properties and the in vitro lung deposition were evaluated using a Dosage Unit Sampling Apparatus and Andersen Cascade Impactor. The powders had a high yield (65-80%), drug content between 170 and 880 mg·g~(-1) and high encapsulation rate (93-97%). All formulations had spherical particles with a rough surface and the primary mean particle size was around 1.00 μm . The formulation prepared with the lowest amount of polymer led to a more symmetric primary particle size distribution and an efficient deagglomeration behavior. The powders exhibited dexamethasone crystallinity and no interaction between the drug and other excipients was evidenced. Dexamethasone release from the powders followed the biexponential model. The lowest drug:polymer ratio led to the best controlled release of the drug. Furthermore, the powders showed dose uniformity close to 100%, a mass median aerodynamic diameter lower than 5 μm and fine particle fraction between 59% and 62%. These polymeric particles (as powders) can be recommended as a platform for the production of new controlled release systems for pulmonary administration.