Validation of the IntelliCap® system as a tool to evaluate extended release profiles in human GI tract using metoprolol as model drug

Abstract

A clinical study was conducted to validate the in vivo drug release performance of IntelliCap® CR capsules. 12 healthy, male volunteers were administered IntelliCap® CR capsules, filled with metoprolol as a BCS 1 model drug, and programmed to release the drug with 3 different release profiles (2 linear profiles extending over 6h and 14h, respectively, and a pulsed profile with two equal pulses separated by 5h) using a cross-over design. An oral metoprolol solution was included as a reference. Standard bioavailability variables were determined. In vivo drug release-time profiles for the IntelliCap® CR capsules were calculated from the plasma drug concentrations by deconvolution, and they were subsequently compared with the in vitro drug release profiles including assessment of level A in vitro/in vivo correlation (IVIVC).The relative bioavailability for the linear, extended release profiles was about 85% which is similar to other extended release administrations of metoprolol. There was an excellent agreement between the predetermined release profiles and the in vivo release for these two administrations. For IntelliCap® CR capsules programmed to deliver 2 distinct and equal drug pulses, the first pulse was delivered as expected whereas only about half of the second dose was released. Thus, it is concluded that the IntelliCap® system is well suited for the fast and reliable generation of in vivo pharmacokinetic data for extended release drug profiles, e.g. in context of regional drug absorption investigations. For immediate release pulses delivered in the distal GI tract this version of the device appears however less suitable.