Development Of Diclofenac Ethanolamine Latex

Diclofenac is a non-selective cyclooxygenase-1/2 inhibitor when tested in vitro, but a slightly preferential cyclooxygenase-2 inhibitor when tested ex vivo. Although it is one of best-tolerated classical NSAIDs, gastropathy appears following chronic oral administration. Then diclofenac ethanolamine transdermal emulgel was prepared in order to reduce the adverse effects after oral administration, and promote drug therapeutic effect and patient complianceIn present study, we synthesized four complexes of diclofenac monoethanolamine, diethanolamine, triethanolamine and N-（2-hydroxyethyl）-piperidine （D-HEPP）, and the complex formation was proved by DSC and FT-IR studies. Comparing with diclofenac, these four complexes have a lower melting point and a higher water solubility, which indicates these complexes should be more suitable for percutaneous absorption than diclofenac free acid.Seven substances which are widely used in pharmaceutical field together with diclofenac free acid were used, including three commercial products of diclofenac diethylamine, sodium and potassium, and four synthesized complexes. The partition coefficient of drugs between stripped skin and emulgel （K_s） was also determined, and a positive relationship was found between Ks and the cumulative amount of drug permeated over a period of 8 h （Q₈） with a correlation coefficient （r） of 0.974. At the same time, we compared their percutaneous absorption through rat skin from one of the topical preparations of emulgel. The flux and Q₈ of diclofenac were increased significantly （P < 0.05） no matter in the form of organic or inorganic diclofenac complexes in the present study. Among the complexes examined, diclofenac ethanolamine （D-E） were found to be the most appropriate form of diclofenac acid to promote drug permeation in our system.The mono-factor method was adopted to optimize the emulgel formulation, and optimal formulation was acpuired with 0.5%Carbomer as mitrix, 4% IPP as oil phase and 4%azone as penetrated enhancer. Our emulgel represented a higher permeability with its flux and Q₈ as 2.89 and 2.75 times higher as that of diclofenac diethylamine emulgel （Votalin）. The experiments was also performed to investigate the quality of emulgel, and our emulgel was testified to be a formulation with a suitable value of pH, good-tolerated properties of centrifugalization,heat and cold, and a steady drug concentration.The pharmacological experiment indicated that diclofenac emulgel（p < 0.001） and diclofenac diethylamine emulgel （Votalin） （p < 0.01） significantly relieved the pain of rats induced by acetic acid aqueous solution, the former was a more efficient one （p < 0.05） compared with the latter, and its pain inhibition ratio was 61.07% and 37.40%, respectively.