Intercalation of the anticancer drug lenalidomide into montmorillonite for bioavailability improvement: a computational study.

Context: Lenalidomide (LEN) is used for the treatment of myeloma blood cancer disease. It has become one of the most efficient drugs to halt this disease. LEN is a low-soluble drug in aqueous media. The search of a pharmaceutical preparation to improve the bioavailability and, therefore, to optimize its efficiency is an important issue for pharmaceutical industries and health care. The use of natural excipients such as montmorillonite (MNT) can provide changes in the physical-chemical properties for improving the bioavailability of this drug. We present the first computational study at the atomic scale of the periodic crystal forms of the polymorphs for this anticancer drug, highly demanded in the pharmacy market. In addition, we propose a pharmaceutical preparation by intercalation of LEN in natural MNT. So, our calculations predict that LEN can be intercalated in the interlayer space of MNT, and be released in aqueous media, and physiological aqueous media in consequence. This release process is a more exothermic reaction than the unpacking energy of any of its polymorphs. Besides, the infrared spectra of the LEN molecule and its crystal polymorphs, and LEN intercalated in the confined space of MNT, have been calculated at different levels of theory. The band frequencies have been assigned, matching with the experimental bands, predicting the use of this technique for experimental studies.

Method: In this work, the method is aimed to explore this research at the atomic and molecular level by using computational modelling methods including INTERFACE FF and other FF along with quantum mechanical calculations (Dmol and CASTEP) of 3-D periodical systems applying periodical boundary conditions. Models of the isolated molecule and two polymorphs of the crystal structures, with the model of bulk water and LEN intercalated in the MNT model, have been considered. An analysis of the intermolecular interactions is accomplished.