Study On The Preparation And Transdermal Penetration Of Diclofenac Sodium Cataplasm In Vitro And In Vivo

Diclofenac sodium, a kind of widely used nonsteroidal antiinflammatory drugs, has a lot of problems, such as having a short biologic half-life, stimulating gastrointestinal tract, causing gastrointestinal disorder, and gastric ulcer. In order to bring its effect into full play, reduce adverse effects, prolong its effect time, the study developed a kind of cross-linking cataplasm of DCS.Firstly, a method for analyzing DCS content with UV spectrophotometry was proposed. This method was accurate, reliable and easy to operate. Some physic-chemical properties of DCS were determined, such as the solubility in different mediums, oil-water partition coefficient. This research provided theory basis for the design and analysis during this study.With selection of each element, choosing sodium polyacrylate NP700 as framework material of cataplasm, Carbopol 980 and CMC-Na as tackifiers, dihydroxyaluminium aminoacetate as cross-linking agent, kaolin as filler, glycerol as humectant, EDTA as cross-linking regulator, PEG400 as defoaming agent. The single factor test and orthogonal test were used to design formulations with tacking strength, holding strength and sensory evaluation as comprehensive indicators.An improved Franz diffusion cell and excised mouse skin were applied, preliminarily studying percutaneous absorption of DCS with different pH and penetration enhancers in vitro with the enhancing rate and lag time as the indicators. The result showed that percutaneous rate of DCS at pH 6.5 was lower than pH 5.5. Compared with the blank group, tween 80 had no significant permeation effect on DCS; azone had a slight effect with longer lag time; oleic acid, menthol and borneol had significant effect on DCS with the content of 3%,3% and 1%, respectively. The result of joint effect of two kinds of penetration enhancers showed that 3% menthol and 1% borneol had the most significant effect.The result of quality evaluation showed that DCS cataplasm developed met the requirements in appearance, formability, ointment content, tacking strength, adhesion, residue and stability with accelerated test for three months. The drug release characteristic of DCS in vitro coincided with the Higuchi model; the percutaneous rate was 110.55μg·cm-2·h-1, and accumulated transmission rate was up to 38.86% for 12h. The research of pharmacokinetics of DCS cataplasm in rabbits showed that the relative bioavailability was 150.30%. And the transmission of DCS in vitro was well correlative with the absorption fraction in vivo.