Herein, we challenged the isolated lung (IL) technique to discriminate the performance of lung-delivered polymeric microparticles (MPs) having distinct drug release rates. For this purpose, sildenafil-loaded poly(lactide-co-glycolide) MPs were administered to the airspace of an IL model and the drug absorption profile was monitored.

MPs (particle size of similar to 5 mu m) composed of PLGA of lower molecular weight (and glass transition temperature) manifested in the most rapid in vitro drug release (half-times ranging from <15 to similar to 200 min). Moreover, micro-encapsulation resulted in a delayed sildenafil transfer over the air/perfusate barrier (half-times ranging from <5 to similar to 230 min), where the actual ex vivo absorption profile depended on the release behavior of the utilized formulation. Finally, the obtained in vitro and ex vivo results were tested for level C, B and A correlations. The plotted data showed good agreement (R-2 > 0.96) and the slopes of the resulting lines of regression (i.e., 0.80-0.85) indicated a slightly elevated in vitro drug release behavior.

Overall, the IL model was able to differentiate between distinct microparticulate formulations and is, therefore, a valuable technique for early testing of potential inhalable controlled release medications. (C) 2016 Elsevier B.V. All rights reserved.