Bioavailability of theophylline-containing poly(methyl methacrylate) microspheres in rabbits

Abstract

Microspheres for the sustained release of theophylline were prepared by a solvent evaporation technique. The release rate of theophylline from the microspheres was determined using a USP paddle-type dissolution apparatus. The in vitro release rates showed marked differences among the microspheres studied. The bioavailability of theophylline released from microspheres in rabbits was studied after a single oral administration. It was demonstrated that the administration of theophylline microspheres prepared with 10% poly(ethylene glycol) 4000 as an additive led to sustained theophylline levels in plasma, which did not show sharp concentration peaks. The time required to reach peak plasma concentrations of theophylline was about 5 hours. On the other hand, microspheres prepared with higher concentrations of poly(ethylene glycol) 4000 induced maximum plasma concentrations after a shorter time. Microspheres prepared with different concentrations of poly(ethylene glycol) showed a better correlation between t 50% and C max and t 50% and AUC 0–∞ than the microspheres prepared with different ratios of drug to polymer. The results show that poly(methyl methacrylate) microspheres containing theophylline offer definite advantages over theophylline in maintaining an effective plasma concentration of the drug.