Stability test of novel combined formulated dry powder inhalation system containing antibiotic: physical characterization and in vitro- in silico lung deposition results

Objective: The aim was to study the stability of dry powder inhaler (DPI) formulations containing antibiotic with different preparation ways - carrier-based, carrier-free, and novel combined formulation - and thereby to compare their physicochemical and in vitro-in silico aerodynamical properties before and after storage. Presenting a novel combined technology in the field of DPI formulation including the carrier-based and carrier-free methods, it is the most important reason to introduce this stable formulation for the further development of DPIs. Methods: The structure, the residual solvent content, the interparticle interactions, the particle size distribution and the morphology of the samples were studied. The aerodynamic values were determined based on the cascade impactor in vitro lung model. We tested the in silico behavior of the novel combined formulated samples before and during storage. Results: The physical measurements showed that the novel combined formulated sample was the most favorable. It was found that thanks to the formulation technique and the use of magnesium stearate (MgSt) has a beneficial effect on the stability compared with the carrier-based formulation without MgSt and carrier-free formulations. The results of in vitro and in silico lung models were consistent with the physical results, so the highest deposition was found for the novel combined formulated sample during the storage. Conclusions: It can be established that after the storage a novel combined formulated DPI contained amorphous drug to have around 2.5 μm mass median aerodynamic diameter and nearly 50% fine particle fraction predicted high lung deposition in silico also.