Effects of the conformation of PLGA molecules in the organic solvent on the aerodynamic diameter of spray dried microparticles

The purpose of this study was to reveal the effects of the conformation of poly (DL-lactide-co-glycolide) (PLGA) molecules in the feed solution on the aerodynamic diameter of PLGA microparticles prepared by using spray drying method. We investigated the conformation of PLGA molecules in the feed solution using viscometry. The data provide information about the polymer coil radius (R_coil), the overlap concentration (c*). Then, we prepared various rifampicin-loaded PLGA microparticles by changing the mixing ratio of dichloromethane and methanol. We used a cascade impactor and mice to measure the aerodynamic diameter of the microparticles in vitro and in vivo, respectively. The viscosity measurement showed that an increased molar ratio of methanol in the solvent compositions resulted in the decreased R_coil and increased c*. Then, we found that the increased molar ratio of methanol in the solvent compositions resulted in the increased fine particle fraction value in vitro and delivery ratio to lung in vivo. The conformation of PLGA molecules in the feed solutions influences PLGA network in the microparticles, which would affect the aerodynamic diameter of the microparticles. In conclusion, the finding of our study suggests that solvent selection and connectivity of PLGA molecules of microparticles are associated with the aerodynamic diameter.