Bumetanide/Synthetic Saponite Composites: Performant Systems for Enhanced Drug Dissolution Rate.

Bumetanide is an efficient diuretic drug with poor water solubility and dissolution rate. In this study, bumetanide/synthetic saponite systems with enhanced solubility and dissolution rate are developed. Different synthetic strategies (hydrothermal and sol-gel) and aluminum contents are explored to prepare saponites with adjustable stacking. Bumetanide loading is achieved by a solution method. The synthetic route is feasible and scalable. Crystalline and non-crystalline bumetanide co-exist in the hybrids, and the non-crystalline fraction prevails in stacked saponite-based composites. Electrostatic interaction occurs between the negatively charged smectite layers and the protonated anilinic group, and the molecules accommodate within the interlayer spacing of stacked saponites. Compared with bumetanide, all the composites improve water solubility, wettability, and dissolution rate in simulated gastric conditions (pH 1.2 and 4.5) and deionized water. The samples with drug intercalation and a reduced fraction of crystalline bumetanide are the best-performing. The drug release is favoured at pH ≥ 4.5, as electrostatic repulsion occurs between the saponite layers and the carboxylate group of bumetanide. The complete release of the bumetanide dose, not achieved in sufficiently short times for all the fluids considered, is reached in the formulation with appropriate excipients. Bumetanide/saponite composites revealed performant and tuneable systems for bumetanide solubility and dissolution rate enhancement.