Preparation of perphenazine/clay minerals nanocomposites for enhanced dissolution rate in aqueous solutions

• Perphenazine is successfully loaded into Laponite, saponite, halloysite nanotubes • Perphenazine loads in different arrangement, depending on the clay • Enhanced drug dissolution rate at the pH of the intestinal tract • The tablet formulation achieves the full drug release within 30 minutes • Drug's dissolution is independent from the variability of the gastrointestinal tract Laponite, natural and synthetic saponite, and halloysite nanotubes are used to develop perphenazine-clay mineral hybrids with enhanced drug dissolution rate. The perphenazine-clay minerals exhibit quite high drug loading (30-40% w/w). The Laponite hybrid shows an interlayer spacing of 18.56 Å, suitable to host either a monolayer or a multilayer arrangement of perphenazine molecules. In the natural saponite composite, perphenazine arranges alongside the silicate sheets, forming a monolayer. In contrast, in the synthetic saponite and halloysite nanotubes hybrids, perphenazine occurs in both crystalline and amorphous forms. Raman spectroscopy shows a weak carrier-drug interaction in synthetic saponite and halloysite hybrids, whereas a stronger interaction occurs in the laponite-perphenazine system. All the investigated hybrid systems display a fast dissolution rate at the pH of the gastrointestinal tract, even though the entire dose does not dissolve completely at neutral pH. Then a tablet formulation containing the perphenazine-natural saponite hybrid was prepared, allowing the entire drug dose to be released within a few minutes, even at neutral pH.