Use of Flow Focusing® Technology to Produce Tobramycin-Loaded Plga Microparticles for Pulmonary Drug Delivery

Lucia      Martin-Banderas; Maria      Angeles Holgado; Josefa      Alvarez-Fuentes; Mercedes      Fernandez- Arevalo

Abstract

In the present work, a promising formulation of an inhaled powder based on tobramycin-loaded microparticles has been reported. Biodegradable microparticles with controlled diameters in the range of 1-5 μm and narrow size distribution were synthesized by Flow Focusing® technology. Particles production was planned and optimized with the aid of a well-established mathematic model. Close agreements between theoretical an experimental sizes were obtained. To deliver a high payload of tobramycin to the lungs, the influence of surfactant concentration, polymer-drug ratio and initial drug concentration were investigated. For chosen formulations, drug delivery profiles were also studied. In some cases, it was found a controlled drug delivery for more than ten days, which could represent an important advance in the treatment of chronic lung infections. Other particles factors affecting deposit of an aerosol in the lung were also studied, such as surface charge and density.

Keywords: Drug delivery systems, Flow Focusing®, microparticles, PLGA, pulmonary administration, tobramycin sulphate, tobramycin, Biodegradable microparticles, tobramycin-loaded microparticles, mass median aerodynamic diameter (MMAD)