Studies On Transdermal Delivery System Of Flurbiprofen

Flurbiprofen, as an inhibitor of prostaglandin synthetase enzymes, is a non-steroidal anti-inflammatory agent which has anti-inflammatory, analgesic and anti-pyretic properties and used in treatment of musculoskeletal and joint disorders.Flurbiprofen eye-drops are used to inhibit intraoperative miosis during eye surgery and to control postoperative inflammation of the anterior segment of the eye.Flurbiprofen was marketed in British,France,Japan,German and United States with tablets and eye-drops.The main adverse effects are gastro-intestinal.In orderto increase the topical concentration of flurbiprofen in inflammatory joint location,provide a consistent drug release and reduce its side effects resulting from oral administration,an effective flurbiprofen gel was formulated and evaluated in vitro and in vivo.A high performance liquid chromatography (HPLC) method was developed to determine the flurbiprofen.The conditions was as follows: Maxima 820 workstation,Hypersil column ODSC₁₈(4.6mm×200mm 5μm),UV detective wavelength 247nm,Flow rate 1.0ml/min,sensitivity 0.01 AUFS Mobile phase is composed of acetonitrile,H₂O,methanol(45:55:1).By which the inerference of impurity may be avoided and there is a good linear relationship between concentration and peak area.Solubility in various solvents of flurbirpofen was determinted,indicating the possibility of transdermal delivery of flurbiprofen.Solubility of flurbiprofen in pH 7.4 Phosphate buffer saline (PBS) is ten times higher than that in water,so PBS was used as receptor solution for in vitro percutaneous penetration experiment.The permiation of flurbiprofen through excised human skin in the presence of several permeation enhancers was performanced with flurbiprofen water solution and modified Franz-diffusion cell.The results show that many of them may enhance the penetration of flurbiprofen to some degrees,especially co-enchancers showedsignificant effect. For example,the transdermal was 43.18 u g.cm"2.h"' and 49.32 u g.cm^.h'1 when the enhancers was l%Lauryl+10%DMSO and 5% urea+ 20%propanediol+5%oleic acid, while 5% urea inhibit the percutaneous penetration of flurbiprofen. In this study, co-ehancers (5% urea+20%propanediol+5%oleic acid) was detemined as the enhancer of flurbirpofen.The optimal formulation of flurbiprofen transdermal gel was obtained by using orthogonal design to study the different influence of each formulation on the release frofile and viscosity of flurbiprofen.Flurbiprofen in transdermal gel was permeated at zero rate,The viscosity of gel comes up to the standard of the pharmacopoeia of People's Republic of China( 1995).The result of adminiseration of the gel in patients indicated that the flurbiprofen TTS acts quickly and would provide a persistent plasma level.