Drug particle size reduction for decreasing gastric irritancy and enhancing absorption of naproxen in rats

Abstract

Gastric mucosal damage, the most common event following oral administration of NSAIDs, is due to a combination of a systemic effect and a high local drug concentration effect. It has been demonstrated in rats that the gastric irritation induced following oral administration of naproxen was decreased by reducing drug particle size from 20–30 μm to 270 nm and stabilizing the particles in suspension with pluronic F-68. The reduction in irritation is attributed to a decrease in the local high and prolonged concentration of naproxen attributable to reduced crystal size. Further the amount of irritation observed with the orally administered nanoparticle formulation is similar to that following intravenous administration of naproxen. The size reduction of naproxen was also associated with an apparent increase in the rate of absorption by approx. 4-fold. The increase in the rate of absorption is attributed to an increase in surface area for dissolution for the NanoCrystal formulation.