A New Hplc Approach for Determination of In-Vitro Solubility of Naproxen Sodium

Naproxen sodium (NAS) is a non-steroidal anti-inflammatory drug used to relieve moderate to severe aches and pains (1-3). Most of its therapeutic activity is probably mediated through prostaglandin synthesis inhibition (1,4,5). Once dissolved in biologic fluids, naproxen and NAS are chemically identical species and have the same biologic properties. Administration of naproxen as the sodium salt, however, permits more rapid absorption from the gastrointestinal tract (1,2,6). Peak plasma concentration is reached in 1 to 2 hours after ingestion of the sodium salt (68). Food reduces the rate but not the extent of absorption (4). Naproxen is extensively metabolized in the liver to 6-O-desmethyl naproxen, which is inactive. Both naproxen and 6-O-desmethyl naproxen are further metabolized to their respective acylglucoronide conjugated metabolites. Approximately 95% of naproxen is excreted in the urine with <1% as unchanged naproxen, <1% as 6-O-desmethyl naproxen, and 66-92% as their glucuronides or other conjugates (1,9). Three percent or less of an administrated dose is excreted in the feces. Naproxen is an acidic drug that is highly bound (>99%) to plasma proteins at therapeutic concentrations. Naproxen has a high therapeutic index and a shallow dose-response curve, so the effect of other drugs on its pharmacokinetics is not likely to have a large clinical impact (1). Chemical structure of NAS is presented in Figure I. Hacettepe University Journal of the Faculty of Pharmacy Volume 28 / Number 1 / January 2008 / pp. 49-62