Effect of drug (core) particle size on the dissolution of theophylline from microspheres made from low molecular weight cellulose acetate propionate.

Three particle sizes (450, 120, and 5 microns) of theophylline were encapsulated in low molecular weight cellulose acetate propionate (intrinsic viscosity, 1.08 dl/g) by the solvent evaporation method. The theoretical drug content for all the batches of microspheres was 50% (w/w). Particle size analysis revealed that about 50% of the microspheres containing the large theophylline crystals (average length of 450 microns) were greater than 500 microns in diameter, whereas only about 35% of the microspheres containing the medium drug crystals (average length of 120 microns) were greater than 500 microns in diameter. The drug content of the larger microspheres prepared from the large drug crystals and the medium drug crystals was much greater than the theoretical drug content (50%, w/w); however, the drug content of all the batches of microspheres containing micronized drug was close to 50% (w/w). Release of the drug in simulated intestinal fluid was very rapid from microspheres containing large and medium drug crystals, while release was slower and more predictable from microspheres made from micronized drug.