(68b) Manufacturing of Biodegradable Drug-Polymer Nanocomposites for Controlled Drug Release by Supercritical Fluid Extraction of Emulsions

Biocompatible and biodegradable polymers such as poly-lactic-co-glycolic acid (PLGA) may be used as pharmaceutical excipients for pharmaceutical applications such as controlled drug release or targeted drug delivery. For such applications, the drug needs to be incorporated in the polymer in the form of composite micro- or nanoparticles for which narrow particle size distributions are desired. There is a need for the development of scalable processes that are compatible with the sensitive materials involved and with the high standards that are requested for product quality.

Supercritical fluids, mostly supercritical carbon dioxide (scCO2), have been applied in a number of different processes aiming at the production of pharmaceutical micro- or nanoparticles. Generally, such processes are characterized by a number of advantages that stem from the application of scCO2; these are typically mild operating conditions, a low consumption of organic solvents and high degree of product purity. Therefore it suggests itself to investigate whether and how such processes may also be applied for the production of drug-PLGA nanocomposites.

Supercritical Fluid Extraction of Emulsions (SFEE) is a novel technique that allows for the manufacturing of such particles. In this process, drug and polymer are mixed in an organic solution that is dispersed in an oil-in-water emulsion stabilized by a suitable surfactant. Then, the emulsion is mixed with scCO2 in order to remove the organic solvent from the emulsion droplets, leading to the co-precipitation of drug and PLGA. Thereby, stable and solvent-free suspensions in water are obtained, and the solidified polymer or composite particles may be recovered upon depressurization.

In the present study, we investigate different methods that may be applied for the incorporation of both lipophilic and hydrophilic drug substances. A further goal of the study is the characterization of particles with respect to the distribution of drug and polymer within the composite structure. Finally, the characterization of the kinetics of drug release from the co-formulation is carried out in vitro, thus assessing its potential performance in in-vivo applications.