An ab initio polymer selection methodology to prevent crystallization in amorphous solid dispersions by application of crystal engineering principles

In this study, a design approach to produce organic systems in which crystallization is prevented was achieved by extending the molecular recognition framework described in the field of crystal engineering to binary amorphous systems. Easily crystallizing, chemically diverse drug-like organic molecules and polymers were employed for proof of concept studies. To assess the potential of the polymers to disrupt drug–drug intermolecular interactions, prospective intra-species hydrogen bonding was evaluated using a variety of approaches. Based on the resultant evaluations, it was possible to arrive at an ab initio rank order of the crystallization inhibiting performance of the polymers for a given compound. The predicted rank order agreed well with the observed crystallization behavior of an extensive experimental dataset. This approach will enable the rational design of multicomponent glassy systems with optimal resistance to crystallization.