Abstract

ETORICOXIB LIPOSOMES LOADED SUSTAINED RELEASE INTRA-ARTICULAR INJECTION

Reshma N. Mirajkar*, Darshan N. Karmankar, Ashwini R. Madgulkar, Pavan P. Khomane and Mrunmayee V. Velapure

ABSTRACT

Intra-articular (IA) drug delivery provides direct access to joint spaces, enhancing targeted treatment while minimizing systemic effects, relevant for conditions like osteoarthritis. Etoricoxib, a selective COX-2 NSAID, has demonstrated effectiveness in treating joint inflammation. However oral administration has been associated with toxicity and frequent injections results in rapid drug clearance with risk of joint infection challenging its effectiveness. These issues can be addressed by innovative approaches like injection hydrogels to obtain sustained release in the joint cavity reducing distribution to non-target organs with decreased frequency of injections. Also particulate drug delivery like liposomes can improve the tissue penetration. Background: This research focuses on the formulation of a novel etoricoxib liposomes loaded sustained release intra-articular injection.Liposomes containing soy lecithin and cholesterol were preparedusing thin film hydration and incorporated into insitu gel forming injection using thermosensitive polymer Polaxomer 407 22% and sustained release polymer HPMC K 100M 0.5% optimized through statistical experiments. The liposomes achieved high entrapment efficiency of 96.4% with particles in the desired size range 1-1.2 μm. A stable sterile injection was formulated with syringibility through 18-22 guaze needle, optimum viscosity and exhibiting a prolonged drug release over 96 hours. The pharmacokinetic studies showed reduction in the Cmax and delayed Tmax in comparison to the immediate-release injection. The invivo studies showed reduced knee swelling in acute inflammation with no noteworthy pathological abnormalities. Combining these liposomes of etoricoxib with an in situ hydrogel holds potential for improved joint disease treatment with fewer side effects. Results: Etoricoxib liposomes loaded sustained release Intra-articular injection was formed. Conclusion: In summary, this study tackled challenges in intra-articular drug delivery using innovative technologies like liposomes and hydrogels. The optimized liposome formulation showed promise in terms of stability, drug entrapment, and compatibility. Combining these liposomes with an in situ hydrogel led to enhanced stability, sustained drug release, and positive outcomes in both pharmacokinetic and pharmacodynamic evaluations. This approach holds potential for improved joint disease treatment with fewer side effects. Further research and clinical trials could advance this novel drug delivery system towards practical therapeutic applications.

Keywords: Etoricoxib, liposome, insitu gel, osteoarthritis, intra-articular injection.