Low Energy Nanoemulsions as Templates for the Formulation of Hydrophobic Drugs

Abstract

AbstractMost small molecule active pharmaceutical ingredients (APIs) are hydrophobic which poses formulation challenges due to their poor water solubility. Current approaches are energy intensive and involve presenting the API in a nanoparticle form that is then combined with other additives into a stable formulation. Here, a bottom‐up and scalable method that formulates nanoparticles (crystalline or amorphous) of poorly water‐soluble APIs directly embedded in composite hydrogel beads is presented. Using nanoemulsions prepared from a low energy method as templates, the flexible approach allows to vary the embedded API nanoparticle size from 100 to 500 nm and the hydrogel bead size from 100 to 1200 µm, and subsequently achieve control over the dissolution kinetics. To better understand the dissolution process, a physical model is build that allows to collapse the kinetic data onto a master curve and predict the dependence of release rates on size of both API nanoparticles and hydrogel beads. Lastly, it is demonstrated that the dissolution kinetics of multiple drugs embedded in the same hydrogel matrix can be tuned simultaneously, an attractive property for commercial multi‐drug dosage applications. The new approach not only leads to process intensification, but also improved performance.