Experimental and Mechanistic Study of the Heterogeneous Nucleation and Epitaxy of Acetaminophen with Biocompatible Crystalline Substrates

Abstract

The presence of different heterogeneous surfaces can directly influence the nucleation kinetics, crystal growth, and morphology of active pharmaceutical ingredients (APIs). However, a mechanistic understanding of heterogeneous nucleation remains lacking. Herein, we report the use of biocompatible crystalline heterogeneous surfaces to enhance the nucleation rates of the model API compound acetaminophen (APAP). We also report experimental and computational studies of the epitaxial growth mechanism of APAP on different substrates. Five crystalline substrates, namely, d-galactose (DGAL), the α and β forms of d-mannitol (DMAN), α-lactose monohydrate (LMH), and xylitol (XYL) were selected because they contain a similar functionality: a high density of hydroxyl groups per molecule. We measured the induction times in the presence of the substrates and used the results to rank the substrates based on their ability to enhance the nucleation of APAP. While all selected substrates enhanced the nucleation rates, XYL w...