Drug encapsulation using supercritical fluid extraction of emulsions

The current work was aimed at evaluating a new method, supercritical fluid extraction of emulsions (SFEE), for the production of composite (e.g., polymer-drug) micro- and nanoparticles, intended for application in sustained-release drug delivery formulations. Using the proposed method, composite particles were obtained, both in a continuous or batch manner by supercritical carbon dioxide extraction of oil-in-water (o/w) emulsions. Model drugs indomethacin and ketoprofen and biodegradable polymers poly(lactic/glycolic) acid and Eudragit RS were used in order to demonstrate the effectiveness of the SFEE process for producing these particles. Stable aqueous suspensions of composite micro and nanoparticles, having sizes ranging between 0.1 and 2 microm were consistently obtained. Emulsion droplet diameter was found to be the major size control parameter. Other parameters investigated included polymer and drug concentrations in solvent and emulsion solvent fraction. The residual solvent content in the particle suspension obtained was consistently below 50 ppm. Standard dissolution tests were used to observe the sustained release phenomenon of the composite particles. The dissolution profile was characterized in terms of the intrinsic dissolution kinetic coefficients taking into account the specific surface area and solubility of the particles. It was observed that the kinetic coefficient parameter for encapsulated drugs was reduced by 2-4 orders of magnitude when compared to the unprocessed drug particles.