Drug release metadynamics simulations with natural micro- and nanostructured excipients
Finding the most efficient and cheapest drug-excipient complex for an increased or modified release kinetics profile of drugs in the body is a current technological challenge in the pharmaceutical industry, especially to improve the treatment of high prevalence and third-country diseases. In this context, it is highly interesting the research on adsorption and diffusion of organic compounds in the surface or internal spaces of clays or related systems. The aim of this proposal is to apply the unique enhanced sampling metadynamics computational tool to properly analyse the processes involved at the nanometric scale, leading not only to rational principles but also to predictions of the pharmaceutical properties. Initially, a computational strategy based on metadynamics simulations will be defined to reproduce known drug release kinetics in drug-clay complexes. A program to automatize all the computations and data management (METADRUG) will be developed after that and in a subsequent step it will be applied to predict unknown release kinetics of relevant drugs from laminar, porous and nanotubular clays. The overall results shall allow determining the clay structural parameters and drug-clay interactions which modulate the release energetics, contributing to the development of new drug delivery systems and novel analysis processed in pharmaceutical technology. The comprehension and accurate prediction of drug increased or modified release phenomena will contribute in this manner to the EU to gain a competitive edge in this area. By means of the proposed project, the fellow will reach a great expertise in the field of Theoretical and Computational Chemistry by strengthening her skills in the use of classical and quantum chemistry methods, acquiring experience with the employment of metadynamics approaches, and learning about programming in Lammps and Plumed. The fellowship will also allow the applicant to develop a promising scientific career to the European level.