DRUG PARTICLE-SIZE REDUCTION FOR DECREASING GASTRIC IRRITANCY AND ENHANCING ABSORPTION OF NAPROXEN IN RATS

Gastric mucosal damage, the most common event following oral administr ation of NSAIDs, is due to a combination of a systemic effect and a hi gh local drug concentration effect. It has been demonstrated in rats t hat the gastric irritation induced following oral administration of na proxen was decreased by reducing drug particle size from 20-30 mu m 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 orall y administered nanoparticle formulation is similar to that following i ntravenous administration of naproxen. The size reduction of naproxen was also associated with an apparent increase in the rate of absorptio n by approx. 4-fold. The increase in the rate of absorption is attribu ted to an increase in surface area for dissolution for the NanoCrystal formulation.