The Binary System of Ibuprofen-Nicotinamide Under Nanoscale Confinement: From Cocrystal to Coamorphous State

Coamorphous systems have gained success in stabilizing amorphous drugs and improving their solubility and dissolution. Here we proposed to confine a binary mixture of drug and coformer (CF) within nanopores to obtain a nanoconfined coamorphous (NCA) system. For proving feasibility of this proposal, a poorly water-soluble drug (ibuprofen) and a frequently used pharmaceutical CF (nicotinamide) were loaded into nanopores of mesoporous silica microspheres. The solid state of NCA system was characterized by differential scanning calorimetry, X-ray powder diffraction, infrared spectrum, and solid-state nuclear magnetic resonance. With large numbers of nanopores, mesoporous silica microspheres appear to be a feasible carrier to transform a cocrystal system into coamorphism by nanoscale confinement. Benefiting from both nanoscale confinement and CF, the NCA system of ibuprofen achieved synchronic increase in dissolution properties and physical stability. Consequently, the NCA strategy is effective in achieving coamorphous state and offers a promising alternative for formulating poorly water-soluble drugs.