Recently, drug formulations formed from polymer excipients has attracted considerable attention as a novel nanoscopic vehicle for the encapsulation and the controlled delivery of water insoluble drugs. Polymer micelles used for such an application are formed by self association of amphiphilic block copolymers in an aqueous environment. The compatibility between the drug and the hydrophobic block of a block copolymer determines the encapsulation efficiency of the micelles, release profile and even the stability of the delivery system. Currently, most of the drug formulations proceed by “trial and error” method with no distinct method to predict the right combination of block copolymers and drugs to give all the desired functional properties. This is simply because such drug delivery systems involve complex intermolecular interactions and geometric fitting of molecules of different shapes. So, in the context of block copolymer design process, quantification and prediction of the interactions between potential block copolymers and the target drug are of great importance. Computer simulations of copolymer/drug mixtures, to predict these interactions between them, can provide an alluring alternative to the cumbersome and expensive “trial and error” type of formulation studies.

In the present work, we report the use of molecular dynamics (MD) simulation to predict the solubility of two water insoluble drugs, i.e., fenofibrate and nimodipine, in a series of self associating PEO-b-PCL block copolymers with combinations of blocks with different molecular weights. The solubility predictions based on the MD results were then compared with those obtained from solubility experiments and those obtained by the commonly used group contribution method (GCM). The results showed Flory-Huggins interaction parameters computed by the MD simulations to be consistent with the solubility data of the drugs/PEO-b-PCL systems while those calculated by the GCM deviate significantly from the experimental findings. We have also accounted for the possibility of drug solubilization in the PEO shell and assessed the effect of both hydrophilic (PEO) and hydrophobic (PCL) drug solubility in PEO-b-PCL micelles. Our results confirm that not only the interaction energy potential but also the local molecular arrangement plays a vital role in the accurate predictions of solubility parameters and Flory-Huggins interaction parameters.