Influence of Drug-polymer Interactions on Drug Transport of Pharmaceutical Polymer Materials

Interactions between drugs and polymers strongly influence the properties, functionality, and permeability of the polymers, and thereby the kinetics of drug transports. The effects of drug-polymer interactions, specifically ionic bonding between ionized drugs and polymers, were investigated in four different polymeric systems and a multifunctional terpolymeric nanoparticle was developed for three different applications: enteric coating for delayed release; microenvironmental pH (pHm) modifier for pH-independent release; and alcohol-resistant material for mitigation of alcohol-induced dose dumping. A mathematical model based on diffusion and ion exchange reaction was derived to describe drug transport of pharmaceutical polymeric films and coating in a finite volume. The model predictions strongly agreed with experimental data of drug loading into Eudragit® RS/RL films. The results demonstrated that transport of anionic drugs in Eudragit® RS/RL polymer-based dosage forms follow diffusion and ion exchange kinetics. A pH-sensitive nanoparticle (TPN) was developed as a new enteric pore former in an ethylcellulose (EC) coating system with superior properties compared to conventional pore formers. Compared to conventional water-soluble pore formers, TPNs demonstrated very low impact on viscosity of EC dispersions, minimal leaching, suitable mechanical properties, and highly pH-dependent permeability. To achieve pH-independent release of weakly basic drugs, TPN was employed as a pHm modifier by incorporating it into EC matrices loaded with verapamil HCl. The results indicated that swelling was not the primarily release mechanism and that ion exchange played a significant role, especially at higher pore former level of TPN. TPN was further developed as an alcohol-resistant material for mitigation of alcohol-induced dose dumping. TPN-EC films showed reduced drug release in alcoholic media for several ionized weakly basic drugs due to ion-dipole interactions between drugs and PMAA groups of TPN. The mathematical model and polymeric materials developed in this work presents significant contributions to the field of pharmaceutics.Ph.D.2021-11-11 00:00:0