Formulation And Evaluation of Topical Aceclofenac Gel Using Different Gelling Agent

Aceclofenac, a non-steroidal anti-inflammatory drug, has been used in the treatment of rheumatoid arthritis and osteoarthritis. In order to decrease the gastric ulcerogenic effects, aceclofenac gels have been developed. This study was conducted to develop a gel formulation of aceclofenac using four types of gelling agents: carbopol, hydroxypropylmethylcellulose(HPMC), carboxymethylcellulose sodium (Na CMC) and sodium alginate. Effect of penetration enhancer (propylene glycol) on the release has been studied. The gels were evaluated for physical appearance, rheological behavior, drug release and stability. The drug release from all gelling agents through a standard cellophane membrane was evaluated using Keshary-Chien diffusion cell. All gels showed acceptable physical properties concerning color, homogeneity, consistency, spreadability and pH value. Among all the gel formulations, carbopol showed superior drug release than followed by Na CMC, HPMC and sodium alginate. Drug release decreased with increase in polymer concentration. Drug release was not linearly proportional with the concentration of penetration enhancer or co-solvents. Stability studies showed that the physical appearance, rheological properties, and drug release remained unchanged upon storage for two months at ambient conditions. *Corresponding author, Mailing address: Mr. Japankumar Arvindbhai Patel M. Pharm (Pharmaceutics) Lecturer, Department of Pharmaceutics Sat Kaival College of Pharmacy, Sarsa Email: japankumarp@yahoo.com Mobile: 09426423394 F u l l L e n g t h R e s e a r c h P a p e r C o v e r e d i n O f f i c i a l P r o d u c t o f E l s e v i e r , T h e N e t h e r l a n d s Article History:-----------------------Date of Submission: 23-10-2010 Date of Acceptance: 25-01-2011 Conflict of Interest: NIL Source of Support: NONE Int. J. Drug Dev. & Res., Jan-March 2011, 3 (1): 156-164 Covered in Scopus & Embase, Elsevier 156 disorders. This route of drug delivery has gained popularity because it avoids first pass effects, gastrointestinal irritation, and metabolic degradation associated with oral administration [1]. Due to the first past effect only 25-/45% of the orally administered dose reaches the blood circulation. In order to bypass these disadvantages the gel formulations have been proposed as topical application [2]. Topical gel formulations provide a suitable delivery system for drugs because they are less greasy and can be easily removed from the skin. Percutaneous absorption of drugs from topical formulations involves the release of the drug from the formulation and permeation through skin to reach the target tissue. The release of the drug from topical preparations depends on the physicochemical properties of the vehicle and the drug employed. In order to enhance drug release and skin permeation, methods such as the selection of a suitable vehicle5, co-administration of a chemical enhancer [3] have been studied. Gel base formulation makes the drug molecules more easily removable from the system then cream and ointment [4, 5]. Gels for dermatological use have several favorable properties such as being thixotropic, greaseless, easily spreadable, easily removable, emollient, nonstaing, compatible with several excipients and water-soluble or miscible [6]. Aceclofenac is chemically [[[2[(2,6,Dichlorophenyl) amino] phenyl] acetyl] oxy] acetic acid [7], is a new orally effective NSAID of the phenyl acetic acid group. It posses a remarkable antiinflammatory, analgesic and antipyretic properties. The continue use of aceclofenac through oral route causes ulcerogenic effect, flatulence, indigestion (dyspepsia), vertigo, dizziness, dyspnoea, stomatitis, itching (pruritis) [8, 9]. When a drug system is applied topically, drug diffuses passively out of its carrier or vehicle. A unique feature of aceclofenacs pharmacology is that it stimulates glycosaminoglycans (GAG) synthesis, which in turns enhances skin permeation of NSAIDs [10]. Aceclofenac when presented in the form of topical gel can reduce local inflammations. Hence for local inflammation or pain in the body, the topical application of aceclofenac may be useful which also avoids the side effects associated with the oral therapy. Hence, a topical ointment containing aceclofenac was prepared [11]. It is established that gel formulations are superior topical formulation over any other topical formulations, because these system have better application property in comparison to creams and ointments [12]. The objective of present study was conducted to develop a gel formulation of aceclofenac using four types of gelling agents: carbopol, hydroxypropylmethylcellulose (HPMC), carboxymethylcellulose sodium (Na CMC) and sodium alginate. Effect of penetration enhancer (propylene glycol) on the release has been studied. The gels were evaluated for physical appearance, rheological behavior, drug release and stability. The drug release from all gelling agents through a standard cellophane membrane was evaluated using Keshary-Chien diffusion cell. MATERIALS Aceclofenac (Gift sample, Aristo Pharma Pvt Ltd, Bombay), carbopol-934, Na CMC salt medium viscosity 200-400 cPs, sodium alginate, propylene glycol, triethanolamine, propylparaben, sodium hydroxide, potassium di hydrogen ortho phosphate, HPMC, Methylparaben (N R Chem, Bombay). EQUIPMENT Digital balance (Shimadzu Corporation, Japan), UV-Visible spectrophotometer (UV-1700A Shimadzu corporation, Japan), pH meter, Magnetic stirrer, Water bath shaker (Servewell Instruments and Equipments Pvt. Ltd.Banglore, India), Brookfield LVDV-II +Pro Viscometer (Brookfield Engineering Laboratories, Inc. USA). Int. J. Drug Dev. & Res., Jan-March 2011, 3 (1): 156-164 Covered in Scopus & Embase, Elsevier Japan Patel et al: Formulation And Evaluation of Topical Aceclofenac Gel Using Different Gelling Agent