(529a) Preparation of Pharmaceutical Micro- and Nano-Composites Using Supercritical Fluid Extraction of Emulsions

Particles of the biocompatible and biodegradable polymer poly(lactic-co-glycolic) acid, PLGA, constitute a widely studied pharmaceutical carrier system used to achieve e.g. controlled release or targeted delivery of active pharmaceutical ingredients. The manufacturing of the corresponding drug-polymer nano-composites represents an interesting challenge to drug formulation technology. The present study evaluates a novel technique for the production of such particles, namely supercritical fluid extraction of emulsions, SFEE.

For SFEE processing, drug and polymer are mixed in an organic solution that is dispersed in water, forming an oil-in-water emulsion stabilized by a suitable surfactant. In a second step, the emulsion is mixed with supercritical CO2, thereby extracting the organic solvent from the emulsion droplets, leading to the co-precipitation of drug and PLGA as composite particles. These form a stable and solvent-free suspension in the inert aqueous phase, from which they may be recovered upon depressurization.

The present study investigates the influence of operating conditions on the achieved particle size distributions. Further, the incorporation of various pharmaceuticals has been achieved by applying different strategies depending on the nature of the drug molecule. For instance, the encapsulation of water-soluble lysozyme may be achieved through double-emulsion and suspension-emulsion systems. On the other hand, hydrophobic compounds such as the anti-inflammatory drug ketoprofen (KET) are encapsulated in PLGA using a common organic solution.

For the latter system, also the product stability in aqueous suspension has been investigated. While composites of KET and PLGA are stable at low KET content, we have observed the recrystallization of KET in supersaturated co-formulations exceeding the solubility limit of KET in PLGA. By equilibration of PLGA particles with KET crystals, the solubility of KET in PLGA may be studied. The method has been used to compare the solubilities of racemic KET and enantiopure S-Ketoprofen, and to assess their dependency on temperature.