Preparation Of Ultra-Fine Naproxen Particles By Anti-Solvent Re-Crystallization

Ultra-fine drugs own many advantages. This paper deals with the preparation of ultra-fine naproxen drug. Naproxen is one of the most important anti-inflammatory drugs and occupies a high market share. It is a kind of poorly water-soluble drug (<1mg/ml) and the solubility is also very low under the gastric juice environment, which effects the drug dissolution rate and bioavailability. The long time usage would stimulate stomach and intestine greatly, limiting the clinic application of naproxen. Therefore, it is very important to prepare ultra-fine naproxen particles.Ultra-fine naproxen particles were synthesized by anti-solvent re-crystallization in beaker. The main factors which influenced the mean particle size and morphology, such as ratio of solvent to anti-solvent, re-crystallization temperature, aging condition and surfactant content, were investigated in detail. SEM, BET, XRD and IR were employed to characterize the as-prepared product and raw drug. The results showed that ultra-fine naproxen particles with a rod-like shape, a width of300～500nm and a length of1～2μm could be prepared under the conditions of the solvent to anti-solvent ratio of LA:LH, re-crystallization of a～b℃, surfactants X content of c～d wt%and aging at e℃for f h. In addition, the crystallization process would not change the drug’s physicochemical properties and crystal form. Due to the smaller particle size, the BET special surface of ultra-fine naproxen was about5.3times as much as that of the commercial crude drug.Based on the above-mentioned results, the scale-up experiment in RPB was performed. The effects of surfactants, temperature and aging condition on the product were examined. The experimental results were basically consistent with those from beaker experiments. There was no change in drug’s physicochemical properties and crystal form, but the particle size is evidently reduced.