MICROENCAPSULATION OF SOLID DISPERSIONS - RELEASE OF GRISEOFULVIN FROM GRISEOFULVIN - PHOSPHOLIPID COPRECIPITATES IN MICROSPHERES

The preparation, characteristics, and behavior of microspheres of poly(L-lactic acid) (PLA) containing griseofulvin (Gris) or Gris:phospholipid coprecipitates are described. Microspheres were spherical and increased in size from 17-mu-m (empty) to 30-mu-m, containing 22% Gris. The release of coprecipitated Gris after 60 min from 146,000 MW PLA microspheres in pH 2.0 buffer at 37-degrees-C was twofold greater than that from microspheres containing pure Gris. Also, the release profile from pure Gris microspheres was 25% lower than its dissolution profile, whereas the dissolution and microsphere release profiles of Gris coprecipitate were the same. Microspheres of Gris coprecipitate suspended in PEG 600 in hard gelatin capsules for 1 week released Gris at levels comparable to the dissolution of coprecipitate. Decreasing the MW of PLA substantially increased the release of Gris from microspheres of coprecipitate after 20 min but insignificantly from microspheres of pure Gris. These findings suggest that microsphere formulation offers some new opportunities in the development of solid dispersions which normally encounter processing difficulties.