Delayed Release of Hydrophilic Solutes from Capsules

Abstract

Hydrophilic small-molecule solutes (e.g., drugs) can be loaded into hydrogels, but the solutes leak out rapidly (in minutes) when the gels are placed in water. Solute release can be completely stopped if the gel is covered by a thin shell of paraffin wax (melting point Tm ~ 57°C); in such ‘capsules’, the wax shell is a hydrophobic solid. Here, we vary the design of our capsules to achieve ‘delayed release’ of solutes into water: i.e., no release for a delay period (6 to 72 h) followed by a slow and sustained release thereafter. The key is to include an additive in the shell that is miscible with the wax but is weakly hydrophilic and has a lower Tm. Examples are fatty acid esters, notably isopropyl palmitate (IPP, Tm ~ 11°C). For example, when a solute-loaded gel is covered by a 80/20 wax/IPP shell, we find a 3-day delay at 25°C before any release, followed by a near-constant release rate (i.e., ‘zero-order’ release) for the next 20 h. The time delay and release rate can be tuned via the concentration and type of additive in the shell. The delayed release occurs because the wax/IPP shell is an inhomogeneous crystal (as wax and IPP are only partially miscible). Our approach can be used to delay the release of dyes, drugs (e.g., diclofenac), and reactive agents (e.g., H2O2) out of the core gel. The simplicity and generality of our approach should make it useful for controlled release applications in the pharmaceutical, agrochemical, and cosmetics industries.