Gg. Liversidge et P. Conzentino, DRUG PARTICLE-SIZE REDUCTION FOR DECREASING GASTRIC IRRITANCY AND ENHANCING ABSORPTION OF NAPROXEN IN RATS, International journal of pharmaceutics, 125(2), 1995, pp. 309-313
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.