Theoretical and experimental investigation on the intercalation of metformin into layered clay minerals

Abstract

This work introduces a comparative study on the use of two layered clays, a natural Wyoming montmorillonite (commercialized as Cloisite®Na; Mt) and a synthetic hectorite (commercialized as Laponite® XLG; Lap), to encapsulate metformin (MF), which is the most widely used oral drug for the treatment of type II diabetes. The aim was the evaluation of the suitability of the synthetic Lap clay as substrate for the controlled release of MF in comparison to the montmorillonite clay previously studied, in view to dispose of a convenient and well-regulated clay-based component for pharmaceutical formulation production. The combination of molecular modeling and experimental characterization techniques, such as FTIR, XRD, CHN chemical analysis and EDX, allowed us to study the adsorption process and the final molecular arrangement of MF in the interlayer space of the two silicates. The intercalation of MF in both clays follows an ion-exchange mechanism that leads to a basal spacing increase of 0.36 nm and 0.40 nm for the Lap-MF and Mt-MF systems, respectively, and the intercalated amount of MF matches the cation exchange capacity of each clay. Calculations at molecular level showed thermodynamically favorable systems produced by cation exchange reaction, where the MF species form a monolayer in the interlayer of both clays. In view to the application of these materials as delivery systems of MF, the release of the drug from Lap-MF and Mt-MF intercalation compounds was evaluated in pH conditions that simulate those of the gastrointestinal tract. Interestingly, Lap-MF allows a complete release of the loaded drug, guaranteeing the possibility of reaching an efficient drug delivery system. However, the large MF release in acid medium in both systems makes necessary a further encapsulation of the intercalation compound in a protective polymer matrix to increase the delivery in the intestine. Promising results were obtained using pectin as encapsulating matrix, leading to a gradual release of MF in the simulated gastrointestinal tract conditions.