Studies on the Influence of Amiodarone Complexation with Cyclodextrin Derivatives on the in Vitro Release from Matrix Tablets

The release of the active substance from the matrix modified-release tablets based on Kollidon SR and chitosan is dependent on its degree of solubility in the dissolution medium as well as on the matrix forming polymers. Through the complexation of amiodarone hydrochloride with hydroxypropyl-β-cyclodextrin, an inclusion complex was obtained that showed an increase in solubility by more than 200%. Matrix tablets were obtained through the direct compression method for both free and complexed amiodarone. The two formulations were comparatively studied in terms of the release kinetics of the active substance using in vitro release testing and the results were analysed by fitting into four representative mathematical models for the modified release oral formulations. The release tests were conducted using a paddle apparatus 2 for a 12 hours total in simulated gastrointestinal fluids: 2 hours at pH 1.2 and then 10 hours at pH 6.8. The released amiodarone from the studied formulations was quantified using a validated HPLC method. Two factors have been calculated to assess the release profile of amiodarone: f2 the similarity factor and f1 the difference factor. Akaike index and the correlation coefficient were the criteria used for selecting the model that most faithfully depicted the release profile of each formulation studied.