ABSTRACT
A floating gastroretentive capsule as one component of a new therapeutic system for the peroral delivery of drugs with specific absorption sites in the upper gastrointestinal tract (GIT) has been developed. The technology has been used to produce a formulation containing the antibacterial drug, amoxicillin. However, the new technology can also be adapted for use with various active pharmaceutical ingredients (API) that require extended and controlled delivery over a period of time. Therefore a new peroral amoxicillin/clavulanaic acid therapeutic system that is composed of an immediate release tablet representing an initial dose of both APIs and a controlled release floating capsule containing additional amoxicillin was evaluated using an in vivo bioavailability study. Several pharmacokinetic (PK) parameters for amoxicillin and clavulanic acid were calculated from the plasma levels. The pharmacokinetic parameters investigated included AUC0-t, AUC0-1, AUC0-t/AUC0-1, Cmax, Tmax, kel and T1/2. In addition the time over which (T4 and T2) the plasma concentration of amoxicillin was above the minimum inhibitory concentration (MIC) was calculated from the resultant plasma levels. Enhanced pharmacokinetic parameters of the newly developed therapeutic system containing 1500mg of amoxicillin and 125mg of clavulanic acid were confirmed. A prolonged time over MIC (T4 and T2) of amoxicillin in relation to a regular immediate release amoxicillin/clavulanate formulation was also confirmed. The
floating gastroretentive capsule and the new therapeutic system are claimed in patent applications WO 2004/058230 and WO 2004/073695 (1,2).
