Cucurbit[n]urils as excipients in pharmaceutical dosage forms

Abstract

Native, unfunctionalised cucurbit[n]urils (n = 6, 7, or 8) have shown enormous potential as excipients in medical formulations for improving drug delivery. Specific benefits include improved drug stability, solubility, controlled or triggered release, taste masking, inducing drug pKa shifts and as antidotes. Base on in vitro and in vivo models, cucurbit[n]urils have been found to have little systemic toxicity, although they do show some specific organ toxicity, and appear to not affect developmental biology. Cucurbit[n]urils readily form hydrates in the solid state, which leads to pseudo-crystal polymorphs that can ultimately affect cucurbit[n]uril–drug complex solubility, bioavailability and through these drug effectiveness. In creating cucurbit[n]uril-based dosage forms, it has been found that the macrocycles can interact with other excipients in the formulation in both the solid state and solution. While the nature of the solid-state interactions are unclear, several studies of solutions have shown that some excipients are incompatible with cucurbit[n]urils as they can cause precipitates and will compete with the drugs for binding within the cavity. To date, cucurbit[n]urils have been formulated into five different dosage forms: oral solid tablet, topical cream, eye drop, implantable hydrogel and nasal insert.