Development of low density azithromycin-loaded polycaprolactone microparticles for pulmonary delivery

作者：Kasten Georgia; Costa Silva Luis Felipe; Lemos Senna Elenara^*

来源：Drug Development and Industrial Pharmacy, 2016, 42(5): 776-787.

DOI：10.3109/03639045.2015.1075032

• factorial design
• controlled release
• polymeric microparticles
• Azithromycin
• pulmonary drug delivery
• double emulsion/solvent evaporation method

Context: The development of low-density polymeric microparticles may be a useful approach to deliver antibiotics such as azithromycin into the lung.
Objective: The aim of this study was to develop azithromycin-loaded low density polycaprolactone microparticles by the double emulsion/solvent evaporation method.
Materials and methods: Microparticles were prepared and characterized according to their physicochemical properties, drug loading, and drug release profiles. A full 2(3) factorial design was used to evaluate the effect of some independent variables on the drug loading and aerodynamic diameter of the particles. An in silico pulmonary deposition model was used to predict the lung deposition profiles for the formulations.
Results and discussion: The resulting particles presented drug loading up to 23.1% (wt%) and mean geometric diameters varying from 4.0 mu m to 15.4 mu m. Bulk and tapped densities were low, resulting in good or excellent flow properties. SEM images showed spherical particles with a smooth surface. However, hollow inner structures were observed, which may explain the low values of bulk density. The estimated aerodynamic diameters ranged from 2.3 mu m to 8.9 mu m. The in silico pulmonary deposition profiles indicated, for some formulations, that a significant fraction of the particles would be deposited in the deeper lung regions.
Conclusions: Statistical analysis demonstrated that not only drug loading but also the aerodynamic diameter of the microparticles is greatly affected by the preparation conditions. Overall, the results indicated that the low-density azithromycin-loaded microparticles with a relatively high respirable fraction may be obtained for the local treatment of lung infections.

• 出版日期2016-5-3