Indomethacin polymeric nanosuspensions prepared by microfujidization

Abstract

Polymeric nanosuspensions containing indomethacin were prepared by a microfluidization-solvent evaporation method. The nanosuspensions were evaluated with respect to total drug content, drug content in the polymer and aqueous phase, particle size, drug crystallization in the aqueous phase, in vitro drug release, and stability to flocculation in 0.1 N HCl and pH 7.4 phosphate buffer. Nanosuspensions with a total drug content of 35 mg indomethacin/ml nanosuspension could be prepared without drug crystallization. More than 98% of the drug were found within the polymer phase. Unwanted drug crystallization in the aqueous phase depended on the drug loading, the drug-polymer compatibility, the organic solvent, and the type and amount of surfactant used. Indomethacin was released rapidly from ethyl cellulose nanoparticles within 15 minutes. Nanoparticles intended to provide drug release over longer periods of time were obtained by using mixtures of ethyl cellulose and poly (methyl methacrylate). In pH 7.4 buffer, anionic, nonionic and macromolecular stabilizers protected the nanosuspensions against flocculation while nonionic surf octants were good stabilizers in 0.1 N HCl.