EFFECT OF PEG-4000 ON THE DISSOLUTION RATE OF NAPROXEN

Naproxen is a nonsteroidal anti-inflammatory drug characterized by its low wettability and poor water solubility. Solid dispersions naproxen :PEG 4000 have been prepared in order to improve the solubility and di ssolution rate of the drug, since these factors can be the limiting st eps for absorption and bioavailability of poorly soluble drugs. X-ray diffraction analysis, infrared spectroscopy and differential scanning calorimetry detected no physico-chemical interaction between the drug and the inert carrier PEG 4000. The phase diagram of the naproxen-PEG 4000 system produced by DSC and hot stage microscopy is reported. The intrinsic dissolution rate of naproxen is calculated. The dissolution kinetics of solid dispersions prepared by the solvent and melt methods are compared with those of free drug and physical mixture. The studie s were carried out at 37 degrees C and pH 1.2 according to the dispers ed amount method. The dissolution profiles obtained indicate that a si gnificant dissolution enhancement occurs with solid dispersions in com parison with the physical mixture. In addition, the physical mixture s howed a dissolution rate higher than the free drug. Dissolution rate c onstants were determined by fitting the experimental data to the cube root function, to get straight line plots.