Revealing the mechanism of polymer inhibition of 2,4-dichlorophenoxyacetic acid Polymorphs phase transition by experimental and molecular dynamics simulation

Abstract

It is well-established that the occurrence of solution-mediated phase transformation makes the precise preparation of pure metastable forms of drugs by solution crystallization methods extremely challenging. This paper demonstrates that the polyvinylpyrrolidone (PVP) and N-vinyl-2-pyrrolidone and vinylacetate (PVPVA) polymers can effectively prevent crystal form transformation of the 2,4-dichlorophenoxyacetic acid (2,4-D) in the solution. We performed the induction time and crystal growth rate experiments at different supersaturation levels. The results showed that the polymer additives can significantly prolong the induction time and have an inhibition effect on crystal nucleation. The PVP and PVPVA almost completely inhibited the crystal growth in both the length and width directions. Molecular dynamics simulations reveal that the interaction energy between the polymer and crystal face determines the magnitude of the inhibition effect on the crystal growth of stable polymorph Form I. These results suggest that polymorph control during the solution crystallization process can be achieved by adding polymer additives.