β-cyclodextrin hinders PLGA plasticization during microparticle manufacturing

Macromolecules, such as poly(lactide-co-glycolide), have nowadays a pivotal role in drug delivery technologies. To have a precise and predictable control of the drug release kinetics in a delivery system, polymer physico-chemical characteristics must be deeply investigated together with all the other components of the device, including the active pharmaceutical ingredient/s. In fact, drug-polymer interaction may result in drastic changes of polymer characteristics. Plasticization, by changing polymer mechanical properties and diffusion coefficients, may seriously compromise device performances. We investigated the possibility to hinder the plasticizing effect of ketoprofen on poly(lactide-co-glycolide) (PLGA) during microparticle preparation. To this aim, ketoprofen was included in β-cyclodextrin and then encapsulated in PLGA. The formation of the inclusion complex was confirmed by X-ray and FT-IR data, and UV-Vis analysis showed that ∼85% of ketoprofen was included in the cyclodextrins. Molecular dynamics forecasted the enthalpy-driven formation of 4 inclusion complexes with hydrogen bonding playing an important role on their stability. PLGA microparticles were prepared using the solvent diffusion/evaporation method with encapsulation efficiency higher than 60%, without polymer plasticization. We proved that ketoprofen/β-cyclodextrin inclusion complex allowed to hinder the plasticizing effect of ketoprofen on PLGA during microparticle preparation. The inclusion of ketoprofen within β-cyclodextrin hindered its physical interaction with the polymer chains thus avoiding plasticization.