Biorelevant Dissolution Testing for the Evaluation of the Release Properties of Interpolymer Complexes Based on Eudragit® EPO and Eudragit® S100 Copolymers

Purpose The aim of this study was to investigate the effect of release media (compendial and biorelevant) in combination with in vitro hydrodynamics on the release of Indomethacin (IND) from interpolymer matrices. Methods Interpolymer complexes (IPC-1, IPC-2 and IPC-3) were synthesized from copolymers Eudragit® grades EPO and S100 which were generously donated by Evonik Rohm GmbH. Indomethacin was selected as a model drug and was purchased from Sigma-Aldrich. The release of IND was investigated in buffer solutions (pH 1.2; 5.8; 6.8 and 7.4) and in biorelevant media (FaSSGF, FASSIF-V2 and FASSCoF) with sequential media change for 7 hours using BIO-DIS Reciprocating Cylinder Apparatus [USP Apparatus III; Agilent Technologies, USA] at 5 dip per minute in 200 ml of medium and Flow through cell apparatus [CE 7 smart USP Apparatus IV; SOTAX, Switzerland] at flow rate 16 ml/min in buffer solutions and 8 ml/min and 4 ml/min in biorelevant media. The concentration of IND was determined by UV-spectrophotometry (Helios, Thermo Electron Corporation, USA) in buffer solutions and by HPLC-UV (Agilent 1200 Series, Agilent Technologies, USA) in biorelevant media. Results The release of IND from the Interpolymer Complexes with the Flow through cell apparatus was negligible in the buffer media with pH value lower than 6.8 and in FaSSGF. Indomethacin was released only in the two last media with pH values of 6.8 and 7.4 in the case of the evaluation of IND in buffer solutions and in FaSSIF-V2 and FaSSCoF in the case of the evaluation of IND in biorelevant media. This profile of release reveals the properties of the formulations tested to have gastro resistant properties and release the drug in the lower part of the intestine. It is important to note that the release of IND from the formulations based on IPC-2 and IPC-3 was similar despite their different compositions and the conditions of their synthesis. In the case of the release evaluation with the Bio Dis apparatus the release profiles of all complexes could show their gastro resistant properties and expected release of IND in the lower part of the intestine only. The release of IND from the formulations of IPC-2 and IPC-3 was similar in the Bio Dis apparatus as observed in the flow through cell apparatus. A higher release of IND was obtained with the BioDis apparatus in all conditions tested due to the disintegration of the matrices observed with this experimental set up. The results of the release studies with the flow through cell apparatus and with the Bio Dis apparatus with sequential media change confirms that all the Interpolymer Complexes tested are erosion type systems. A higher release of IND was observed from formulations based on IPC-1 under all conditions tested. Conclusion IND formulations based on interpolymer complexes Eudragit EPO/S100 provided release of the drug in the lower part of the intestine based on release studies under physiological relevant conditions. IND release was higher from formulations based on IPC-1, whereas IND release from formulations based on IPC-2 and IPC-3 was similar in all conditions tested.