The Delivery of Triamterene by Cucurbit[7]uril: Synthesis, Structures and Pharmacokinetics Study

In recent years, cucurbit[7]­uril (CB[7]) has attracted great attention in drug delivery. Though the effect of CB[7] in enhancing the solubility of water insoluble drugs has been validated, the underlying mechanism remains poorly understood, particularly at a molecular level. This study is designed to evaluate a CB[7]-based pharmaceutical formulation to improve solubility and bioavailability of triamterene (a mild potassium-sparing diuretic). Two polymorphs of triamterene@CB[7] were obtained, and their crystal structures were determined by single crystal X-ray diffraction. The CB[7] molecule forms a stable host–guest complex with triamterene (<i>K</i>_a = 1.69 ± 0.34 × 10⁴ M^–1) in aqueous solution (pH = 1.0). The results of dissolution study demonstrate that the apparent solubility value of triamterene@CB[7] complex in 0.1 M HCl is 1.6 times as large as that of triamterene, while free triamterene was released from triamterene@CB[7] complex in phosphate buffer of pH 6.8. Pharmacokinetic studies in rats reveal that the AUC_0–∞ value of triamterene@CB[7] complex increases 2.8-fold compared with that of free triamterene, and <i>t</i>_1/2 is prolonged from 1.42 to 2.61 h (<i>P</i> < 0.05) after oral administration. The increased solubility and oral bioavailability are attributed to the formation of a hydrophilic capsule composed of two CB[7] molecules, in which two insoluble triamterene molecules are encapsulated. These results demonstrate that triamterene@CB[7] complex is a stable and effective pharmaceutical formulation