ISPUB.COM The Internet Journal of Pharmacology Volume 6 Number 1 1 of 8 Evaluation of Topical Gels Containing Non-Steroidal Anti- Inflammatory Drugs on Inflammation and Hyperalgesia in rats S Padi, M Gupta, J Kehal, A Aggarwal, N Kumar, R Marwaha Citation S Padi, M Gupta, J Kehal, A Aggarwal, N Kumar, R Marwaha. Evaluation of Topical Gels Containing Non-Steroidal Anti- Inflammatory Drugs on Inflammation and Hyperalgesia in rats. The Internet Journal of Pharmacology. 2007 Volume 6 Number 1. Abstract The systemic use of non-steroidal anti-inflammatory drugs (NSAIDs) which act by inhibiting cyclooxygenase (COX) is severely hampered by gastric and peptic ulcers. The topical delivery of NSAIDs has the advantages of avoiding gastric and peptic ulcers and delivering the drug to the inflammation site. There are no studies that compared the pharmacological profile of gel formulations containing different NSAIDs. Therefore, attempt has been made to study the anti-inflammatory and antihyperalgesic effects of NIZER gel (nimesulide, a preferential COX-2 inhibitor, 1 mg per 100 mg gel) and VOVERAN Emulgel (diclofenac sodium, a nonselective COX (COX-1/2) inhibitor, 1 mg per 100 mg gel) in carrageenan-induced inflammation and hyperalgesia in rats. A 100 mg of NIZER gel or VOVERAN Emulgel when applied topically 30 min before inflammogen administration showed marked anti-inflammatory and antihyperlagesic effects against carrageenan-induced inflammation in rats with more significant effect was observed with NIZER gel. The results indicate that gels containing a preferential COX-2 inhibitor are better than a non-selective COX-1/2 inhibitor in alleviating inflammation and hyperalgesia. INTRODUCTION Non-steroidal anti inflammatory drugs (NSAIDs) are widely used for the treatment of fever, acute and chronic arthritic conditions. They act by inhibiting cyclooxygenase (COX) thereby reducing the release of prostaglandins (PGs), well known inflammatory and nociceptive mediators (Dirig et al., 1998; Padi and Kulkarni, 2004; Padi et al., 2004). PGs are gastroprotective in that they enhance the synthesis mucosa, bicarbonate secretion and reduce the gastric acid secretion. However, their systemic use is often limited because of severe upper gastrointestinal ulcers and other side effects (Watson et al., 2000; Padi et al., 2004; Ray et al., 2007; Süleyman et al., 2007). Thus, pharmaceutical dosage forms that deliver drugs to the inflammation site at a sustained, concentrated level over an extended period of time without altering pharmacodynamic activities have the advantages of avoiding the systemic side effects. In the recent time, transdermal drug delivery systems have gained much importance for local but sustained action of many therapeutic agents including anesthetics and analgesics. Most importantly, NSAIDs are incorporated in topical formulations that are designed to deliver drugs at appropriate rates to maintain minimum plasma drug levels for therapeutic efficacy by using skin as the port of entry of drugs (Bhaskaran et al., 2000; Brown et al., 2006; Gupta et al., 2008). One side the topical applications of the drug offer the potential advantages of delivering the drug directly to the site of action and delivering the drug for extended period of time at the inflammation site that mainly acts at the joint and the related regions. On the other hand, topical delivery system increases the contact time and mean resident time of drug at the applied site leading to an increase in local drug concentration while the pharmacological activity of gel formulations may not change as rapidly as the solution form (Brown et al., 2006; Kumar and Philip, 2007). It is well known that transdermal gels are more popular among all topical preparations due to ease of application and better percutaneous absorption than other semisolid dosage forms. The effect of various excipients added in varied concentrations on transcutaneous drug permeation has been explored where the permeation rate of a topical agent may be influenced by drug-vehicle, drug-skin and vehicle-skin interaction (Giannakou et al., 1995; Wu et al., 2000; Omidian et el., 2007). Numerous studies exist in the