ABSTRACT
In the last decade, the use of molecular dynamics (MD) simulations has become more and more familiar to pharmaceutical developers, for example, by checking on polymorphisms [1,2] and calculating properties of host-guest complexes [3,4]. Furthermore, MD simulations can assist dosage form development by predicting valuable physicochemical properties such as viscosity of solutions [5], diffusivity [6], and water adsorption [7]. However, the above-mentioned parameters are often limited to “small” systems either related to the molecular weight of the drug compound and/or the excipient used. The aim of our study is, therefore, to žnd in silico test models using MD methods for polymers, excipients, drugs, and mixtures thereof exceeding standard MD applications in complexity and, hence, facilitates preformulation even at a stage where drug compound or polymer is in an in silico stage of development. Moreover, the risk of unexpected physical or chemical incompatibilities (e.g., immiscibility) during the formulation process, which is time consuming and expensive [8], might be decreased. Fortunately, molecular simulation offers the possibility to calculate many relevant physical properties of the desired excipient and drug molecules as well as of the polymer without the need for costly experiments.
