Bioavailability study of a theophylline oral controlled release capsule containing film coated mini-tablets in beagle dogs

Abstract

Multiple-unit oral controlled release capsules of theophylline containing film-coated mini-tablets exhibited the desired in vitro release characteristics. Certain of these were subjected to single-dose in vivo studies in beagle dogs in a cross-over manner. Hard gelatin capsules each contained a specific number of uncoated and/or film-coated mini-tablets. Individual mini-tablets weighed 15 ± 0.5 mg and were 0.3 cm in diameter. Two experimental formulations (A and B) as well as parallel studies using a 300 mg oral dose of anhydrous theophylline and a commercial controlled release product (Theo-Dur 300 mg) were tested. Formulations A and B each contained 10 uncoated tablets and 10 film coated with Eudragit RS 2% or Eudragit RL 2%, respectively. After oral administration various pharmacokinetic parameters such as AUC, t max and C max were calculated and compared. Formulation B had certain advantages over Theo-Dur in that it had a greater extent of bioavailability, faster onset of action, more constant serum concentrations and serum levels remained above 7 μg/ml for 9.3 h as compared to Theo-Dur (7.9 h).