Molecular Interactions between APIs and Enteric Polymeric Excipients in Solid Dispersion: Insights from Molecular Simulations and Experiments

Solid dispersion of poorly soluble APIs is known to be a promising strategy to improve dissolution and oral bioavailability. To facilitate the development and commercialization of a successful solid dispersion formulation, understanding of intermolecular interactions between APIs and polymeric carriers is essential. In this work, first, we assessed the molecular interactions between various delayed-release APIs and polymeric excipients using molecular dynamics (MD) simulations, and then we formulated API solid dispersions using a hot melt extrusion (HME) technique. To assess the potential API–polymer pairs, three quantities were evaluated: (a) interaction energy between API and polymer [electrostatic (E(coul)), Lenard-Jones (E(LJ)), and total (E(total))], (b) energy ratio (API–polymer/API–API), and (c) hydrogen bonding between API and polymer. The E(total) quantities corresponding to the best pairs: NPX-Eudragit L100, NaDLO–HPMC(P), DMF–HPMC(AS) and OPZ–HPMC(AS) were −143.38, −348.04, −110.42, and −269.43 kJ/mol, respectively. Using a HME experimental technique, few API–polymer pairs were successfully extruded. These extruded solid forms did not release APIs in a simulated gastric fluid (SGF) pH 1.2 environment but released them in a simulated intestinal fluid (SIF) pH 6.8 environment. The study demonstrates the compatibility between APIs and excipients, and finally suggests a potential polymeric excipient for each delayed-release API, which could facilitate the development of the solid dispersion of poorly soluble APIs for dissolution and bioavailability enhancement.