Application of Box–Behnken Design in the Optimization and Preparation of Salicylic Acid Nanopowder using Solvent-Free Green Mechanochemical Approach

BACKGROUND: One of the imperative progressions within the pharmaceutical industry, especially drugs, is the expanded utilization of materials in order to enhance its dissolution, solubility and bioavailability. Planetary ball monomill approach can be the latest entrant to Green nanotechnology – being solvent-free, eco-friendly, cost-effective, and sustainable particle size reduction approach. OBJECTIVES: Salicylic acid nanopowder (SA-NP) was aimed to be prepared using planetary ball monomill by dry milling technique to enhance its solubility and bioavailability. METHODS: Various milling parameters such as milling speed, milling time and number of balls was varied and their effect on dependent responses including size (nm) and polydispersity indices (PDI) were evaluated using a 3–Factorial-3–Level Box-Behnken statistical design. Particle size and PDI analysis was performed using light scattering technique. RESULTS: The particle size of salicylic acid obtained by optimizing the dry milling parameters was Z-Average (d.nm): 776.3 nm and PDI: 0.600 up to Z-Average (d. nm): 205.0 nm and PDI: 0.383. CONCLUSIONS: Dry milling can be used for the preparation of nanopowders of drug candidates with poor water-solubility issues. Present day medications have nano-scaled active ingredients which are rapidly absorbed by the human body as compared to the conventional ones. Enlarged surface area increases the solubility of the drug, thereby improves its bioavailability.