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To investigate the influence of polymer coating on the release of tramadol from a controlled-release tablet formulation (Tramadol-SR), an in vitro dissolution study was carried out. The dissolution rates of this formulation were compared with those of two immediate-release tablets of tramadol (Tramadol-IR) of identical drug loading and drug release properties. The differences in dissolution rate between Tramadol-SR and Tramadol-IR tablets are explained by the dissolution of the coating material and the release of the drug following diffusion of the drug from the tablet core. In vivo bioavailability experiments on six male volunteers were conducted with four study designs using a multiple-dose, crossover trial design (i.e. two treatment periods separated by a washout period of 6 days). In each treatment period, two single doses of Tramadol-SR (37.5 mg and 50 mg) and two single doses of Tramadol-IR (37.5 mg and 50 mg) were administered. The plasma levels of tramadol and its principal metabolite (+)-O-desmethyltramadol were analysed by HPLC. A significant increase in the area under the drug plasma concentration-time curve (AUC) of tramadol was observed in the Tramadol-SR dose groups compared with the Tramadol-IR dose groups. The extent of this increase was approximately 50%, which corresponds to a tripling of the Cmax. The total systemic exposure (AUC0-infinity) of tram