Preparation, optimization and evaluation of transdermal therapeutic system of celecoxib to treat inflammation for treatment of rheumatoid arthritis

Abstract

The purpose of present study was to prepare transdermal therapeutic system that could enhance dissolution of poorly aqueous soluble drug Celecoxib and thus increase its skin permeation. Solubility studies screened triacetin as oil, cremophor RH 40 as surfactant and Polyethylene Glycol 400 as co-surfactant. Pseudoternary phase diagrams were constructed to find out microemulsion region. Independent variables (oil, Smix and water) concentration was used at high (+1) and low levels (-1) that would generate 17 different combinations of microemulsions. Microemulsions were characterized, optimized and evaluated. pH, viscosity, conductivities, refractive index, droplet size and poly-dispersity-index was investigated. Prepared microemulsions were oil in water, thermodynamically stable, isotropic, transparent, deflocculated and within narrow range of size. Mathematical equations and response surface plots related the independent and dependent variables. Optimum microemulsion ME₆ was further incorporated with carbomer 940 gel base to produce microemulsion based gel. ME₆ and its gel showed significant difference (p<0.05) from control gel. Stability studies showed prepared MEBG of celecoxib was stable during storage period. Skin irritation studies found the gel was safe and non-irritating to skin. Anti-inflammatory studies showed significant difference (p<0.05) compared to control gel. Thus, the therapeutic system was successfully developed and optimized using Box Behnken statistical design.

Key words
Anti-inflammatory studies; Celecoxib; franz diffusion cell; microemulsion; transdermal therapeutic system