Highly water-soluble dapsone nanocrystals: Towards innovative preparations for an undermined drug

Dapsone (DAP) is a dual-function drug substance; however, its limited water solubility may impair its bioavailability. Drug nanocrystals are an alternative to overcome this limitation. Herein, a DAP nanosuspension was prepared using a design space approach aiming to investigate the influence of raw material properties and process parameters on the critical quality attributes of the drug nanocrystals. Optimized nanocrystals with 206.3 ± 6.7 nm using povacoat™ as stabilizer were made. The nanoparticles were characterized by dynamic light scattering, laser diffraction, scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, and saturation solubility. Compared to the raw material, the nanocrystals were 250-times smaller. Meanwhile, its crystalline state remained basically unchanged even after milling and drying. The nanosuspension successfully maintained its physical stability in long-term and accelerated stability studies over, 4 and 3 months. Furthermore, toxicity studies showed low a toxicity at a 20 mg/kg. As expected for nanocrystals, the size reduction improved saturation solubility 3.78 times in water. An attempt to scale up from lab to pilot scale resulted nanocrystals of potential commercial quality. In conclusion, the present study describes the development of dapsone nanocrystals for treating infectious and inflammatory diseases. The nanocrystal formuation can be scaled up for commercial use.