Pharmaceutical cocrystals prepared with a cucurbit[8]uril framework for intestine-targeted drug delivery

Abstract

Encapsulation of active pharmaceutical ingredients (APIs) in carrier materials for controlled delivery in the desired site is of paramount importance for optimizing the effectiveness of a therapeutic drug while minimizing its side effects. Cucurbit[8]uril (CB[8]) is herein assembled as a host framework to accommodate APIs (tryptophan, phenylalanine biapenem, and diclofenac sodium) in aqueous solution under room temperature to enhance their stability in the gastric acid and realize sustained release in the intestinal tract. Host-guest interactions were investigated by UV-vis spectroscopy while crystal structures of the supramolecular assembly were determined by single-crystal x-ray analysis, which reveals that both the CB[8] framework crystals and the API@CB[8] cocrystals belong to a monoclinic crystal system. With their aromatic rings folded inside the macrocyclic cavity of CB[8] and their alkyl chains stretching outside to interreact with the carbonyl portals of CB [8] through ion-dipole interactions and hydrogen bonding, both hydrophic and hydrophobic APIs were readily encapsulated inside the supramolecular framework. In comparison to API in its free form, an accelerated dissolution kinetic of the API@CB[8] cocrystals was observed at intestinal pH (6.8), which otherwise demonstrated a lower dissolution profile at gastric pH (1.5). With their biocompatibility confirmed by cytotoxicity test, the proposed pharmaceutical cocrystals provide a new paradigm for intestine-targeted drug delivery.