In vitro - in vivo evaluation of a new oral dosage form of tramadol hydrochloride--controlled-release capsules filled with coated pellets.

The aim of this study was an in vitro - in vivo evaluation of a new oral dosage form of tramadol hydrochloride (TH), controlled-release capsules filled with coated pellets, 100 mg (TC), compared to the sustained release tablets, Tramal Retard, 100 mg (TR). In vitro release study of both formulations showed a similar release profile of TH over 8 h (f2 was 52). In vivo study (single oral, 100 mg dose administration in 8 rabbits) showed that the amount of TH absorbed into the systemic circulation after TC and TR administration was also similar (90% CI for AUC(0-t) and AUC(0-infinity) were 90-124% and 97-109%, respectively). However, a comparison of AUC(0-t) of pharmacokinetics of TC and TR indicates significantly prolonged absorption and elimination processes of TH when the drug is given in controlled-release capsules filled with coated pellets. It was manifested by longer: mean absorption time (p = 0.0016), mean residence time (p = 0.0268), absorption half-life (p = 0.0016), elimination half-life (p = 0.0493) and lower: absorption rate constant (p = 0.0016), elimination rate constant (p = 0.0148) and total body clearance Cl/F (p = 0.0076). It may be concluded that the new TH formulation could be expected to have a more prolonged analgesic activity than commercial sustained release tablets.