In Vitro and in Vivo Evaluation of Transdermal Absorption of Naproxen Sodium

Naproxen sodium is a non steroidal antiinflammatory drug, used in the treatment of inflammatory and degenerative disorders of the musculoskeletal system. It is widely prescribed for the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, gout, extra-articular disorders, bursitis, tendonitis, and non articular rheumatic condition. Naproxen sodium has some side effects when taken orally, epigastric pain, heartburn, nausea, diarrhoea, vomiting, peptic ulcer, and hepatic impairment. The aim of this study was to formulate topical gel containing 1% of naproxen sodium using various ratios of different type of gel forming agents as pectin, hydroxypropylmethyl cellulose low and high viscosity (HPlv&hv), carboxymethyl cellulose (CMC), and carbopol 934 with and without penetration enhancers; isopropyl myristate (IPM) and sodium lauryl sulphate (NaLS). Also the duration of anti-inflammatory activity of new gel formulation of 1% naproxen sodium was measured using carrageenan-induced paw oedema in rats. Furthermore, the pharmacokinetics percutaneous absorption of 1% naproxen sodium from three different gel formulations prepared with pectin, HPlv and carbopol as gel forming agent without penetration enhancers, was studied in six healthy human volunteers. While orally administered naproxen sodium tablet (marketed as Naprofen®) was used as a control. Bioavailability was estimated from plasma concentration which determined up to 72 hr after drug administration. The drug plasma concentration was higher from pectin gel (15.944μg.hr/ml) followed by HPlv (14.4199μg.hr/ml) then carbopol (8.5781μg.hr/ml) with the corresponding rate of drug elimination (Kel) of 0.085 hr , 0.13hr and 0.11hr respectively. The PK parameters, such as the -1 -1 -1 m ax m ax maximum blood concentration (C ), time to reach the peak blood concentration (T ), mean 0– 1/2 residence time (MRT), area under the curve (AUC ) and terminal elimination half-life (t ) were significantly (p <0.001) different following transdermal administration of 1% naproxen sodium gel prepared with pectin without penetration enhancers compared with oral administration of reference naproxen sodium tablet Naprofen®.