Preparation and evaluation of anti-inflammatory activity of gugulipid-loaded proniosomal gel.

Gugulipid is an ethyl acetate extract of guggul resin, obtained from Commiphora wightii (Fam.: Burseraceae) and is official in Indian Pharmacopoeia (1). The active constituent of gugulipid is guggulsterone (4,17(20)-pregnadiene3,16-dione) (2), which is present in a concentration of 4.0ñ6.0%.The guggulsterone is present in guggulipid in the form of stereoisomers E-guggulsterone and Z-guggulsterone. Pharmacokinetic studies conducted in rats after intravenous and oral administration indicated that the absolute bioavailability of the guggulsterone after oral administration was 42.9%. Further, it was observed that in vivo Z-guggulsterone isomerizes to give E-guggulsterone (3). Gugulipid is a potent hypolipidemic agent. Apart from its hypolipidemic activity, a large number of therapeutic activities like antimicrobial, anthelmintic, anti-inflammatory, antiarthritic and antioxidant have been reported (4ñ6). A wide range of therapeutic activities, low bioavailability and aqueous insolubility of guggulipid prompted us to explore an approach, which in addition to removing its undesired pharmacological action also improves its therapeutic concentration at the site of inflammation. Topical application of anti-inflammatory agents at the site of inflammation can overcome their systemic side effects and improve their therapeutic activity. Proniosomal gels have earlier been reported to enhance the topical delivery of levonorgesterol and estradiol (7, 8). Proniosomal gels are the formulations, which on in situ hydration with water from the skin are converted into niosomes. Proniosmal gels overcome the disadvantage of vesicular instability associated with niosomes. The drug entrapped in the niosomal vesicles penetrates the skin at a faster rate than the free drug (9ñ11). Thus, taking view of the topical delivery potential of the proniosomal gel, a guggulipid loaded proniosomal gel based formulation was developed in the present study. The formulated proniosomal based gel formulation was characterized for particle size entrapment efficiency, in vitro drug release and in vivo anti-inflammatory activity using carrageenaninduced rat hind-paw method (12, 13).