Current Drug Delivery, 2005, 2, 223-233 223 1567-2018/05 $50.00+.00 © 2005 Bentham Science Publishers Ltd. Transdermal Delivery of An Analgesic Agent Using Elastic Liposomes: Preparation, Characterization and Performance Evaluation Subheet Jain 1 , N. Jain, D. Bhadra, A.K. Tiwary 1 and N.K. Jain* *Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar [M.P.], 470 003 India, 1 Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Pun- jab, 147002, India Abstract: The aim of the present study was to prepare and characterize novel vesicular carrier elastic liposomes, of most commonly used non-steroidal anti-inflammatory agent diclofenac for its sustained and targeted delivery. Elastic liposomes of diclofenac were prepared and characterized in vitro and in vivo. The effect of different formula- tion variables like type of surfactant, concentration of surfactant and dose of drug on transdermal flux, amount of drug deposited into the skin, muscle and plasma concentration was investigated. The biological activity of opti- mized formulation was evaluated using carrageenan induced rat paw edema model and results were compared with commercial hydrogel formulation. The elastic liposomal formulations achieved muscle drug concentration between 2.2 ± 0.14 to 5.3 ± 0.22 μg/g at 12hr. The same dose of commercial hydrogel formulation produced drug levels be- tween 0.41 ± 0.07 to 1.1 ± 0.09 μg/g in the muscle. Plasma concentration study showed regiospecificity of elastic liposomal formulation. The results of in vivo study revealed that incorporation of diclofenac in elastic liposomes increased its biological activity two fold as compared to commercial hydrogel formulation. The results of the pre- sent study demonstrated greater effectiveness of dermaly applied diclofenac elastic liposomal formulation in com- parison to conventional delivery system. The optimized elastic liposomal formulation offers a promising means for the non-invasive treatment of local pain and inflammation by topical application. Keywords: Skin, Percutaneous absorption, Elastic liposomes, Sustained, Targeted, Transdermal delivery, Biological activity, Regiospecificity. 1. INTRODUCTION Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce inflammation and pain. NSAIDs inhibit cyclooxygenase-2 at the inflammation site, but, un- fortunately, most of them also inhibit gastric mucous cy- clooxygenase-1, which produces gastric damage [1]. Di- clofenac is a non-selective cyclooxygenase-1/2 inhibitor when tested in vitro, but a slightly preferential cyclooxy- genase-2 inhibitor when tested ex vivo. Although it is one of best-tolerated classical NSAIDs, gastropathy appears follow- ing chronic oral administration. Gastrointestinal side effects such as bleeding, ulceration or perforation of the intestinal wall are commonly seen when drug is administered orally. To avoid these adverse effects researchers have used alternate routes of administration [2]. Therefore, an improved diclofenac formula with a high degree of skin permeation could be useful in the treatment of not only locally inflamed skin tissues, but also inflamma- tory and painful states of supporting structures of the body—bones, ligaments, joints, tendons and muscles [3]. The main problem in the transdermal delivery of diclofenac is poor skin permeability rate and rapid elimination from the skin due to its hydrophilic nature. To increase the skin per- meability of diclofenac several approaches were used in past *Address correspondence to this author at the Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar [M.P.], 470 003 India, E-mail: jnarendr@yahoo.co.in; subheetjain@rediffmail.com e.g. Nishihata et al. [4] have reported the promoting effect of ethanol on percutaneous absorption of diclofenac. Obata et al. [5] studied the combined effect of cyclic monoterpenes and ethanol on percutaneous absorption of diclofenac; but these approaches were not able to solve the problem com- pletely and have limitations like skin irritation, limited skin permeability, rapid drug elimination and low skin/blood ratio leading to systemic side effect. To overcome the difficulties of poor skin permeability, recently two vesicular carrier systems elastic liposomes and ethosomes [6, 7] have been reported for effective transdermal delivery of drug. A new type of drug carrier elastic liposomes can circumvent this problem by providing non- invasive delivery of the pharmaceuticals across the skin. At first glance elastic liposomes appear to be remotely related to lipid bilayer vesicles, liposomes. However, in functional terms elastic liposomes differ vastly from conventional liposomal formulation in that they are much more deform- able and adaptable. The extremely high flexibility of their membrane permits elastic liposomes to squeeze themselves, even through pores much smaller than their own diameter under the influence of the transcutaneous hydration gradient. The process is controllable by formulation/administration parameters and provides a good basis for the topical as well as systemic therapy. We had reported earlier elastic liposomes as a carrier for topical delivery of analgesic agent [8-10] and for systemic delivery of contraceptive and anti- HIV agent [11, 12]. The results of the previous study dem- onstrated that analgesic elastic liposomes could penetrate