The manufacturing and stability of composite nanoparticles of the non-steroidal anti-inflammatory drug Ketoprofen (KET) and the amorphous biodegradable polymer poly-lactic-co-glycolic acid (PLGA) has been investigated. Co-formulation particles ranging between 100 and 200 nm in size were produced by supercritical CO2 extraction of emulsions. During I week of storage in aqueous suspension, the composite particles were isolated and analyzed in order to determine the evolution of drug content. In suspensions equilibrated with crystals of racemic KET, particles were observed to approach a KET level of approximately 5 t.%, independent of their initial drug content. Only in the absence of KET crystals, clearly higher drug levels of up to 10 wt.% were maintained during storage. This behavior is rationalized assuming a solubility of approximately 5 wt.% for KET in PLGA together with a metastable zone extending to levels of at least 10 wt.% Using a simple lattice model, a negative value of the dimensionless Flory-Huggins interaction parameter lying in between -0.17 and -0.26 was determined from the solubility, indicating the presence of strong molecular interactions between drug and polymer. (C) 2009 Elsevier B.V. All rights reserved.