Theoretical Considerations of Drug Release from Submicron Oil in Water Emulsions

Abstract

Submicron sized emulsion droplets possess a significantly greater interfacial area per unit volume than a corresponding coarse emulsion. Therefore, processes such as drug binding to surfactants at the O/W interface and interfacial activity of the drug may be operative to a greater extent in submicron systems. This may allow more drug mass to be associated with the nondiffusible droplet than partitioning processes alone would predict. Thus, in order to evaluate and predict drug release from submicron emulsion systems in a nonempirical manner these processes must be considered. Several interfacial and partitioning processes are incorporated into a mathematical model describing the in vitro diffusion of drug from a submicron emulsion across a semipermeable membrane. Drug ionization and its effect on charge dependent interfacial, partitioning, and mass transport processes are considered. Independent kinetic and thermodynamic evaluations of interfacial adsorption processes are experimentally accessible. Initial drug release studies using sulfathiazole as a weakly acidic model compound are consistent with the model.