Diclofenac The Fen Acid Alkyl Amine Salt Preparation And Percutaneous Absorption Studies Of The Patch

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the drugs most commonly used to reduce inflammation and pain. NSAIDs inhibit cyclooxygenase-2 at the inflammation focus, but, unfortunately, most of them also inhibit gastric mucous cyclooxygenase-1, which produces gastric damage. 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 .Therefore, many improved method applied with a high degree of skin permeation could be useful in the treatment of not only locally inflamed skin tissues , but also inflammatory and painful states of supporting structures of the body—bones, ligaments, joints, tendons and muscles.Improvement of the physicochemical properties of drugs is a common approach to optimizing their bioavailability and decrease their side effect. Salt formation is a commonly used method for enhancing the solubility and dissolution rate of poorly water soluble weak electrolyte drugs. Diclofenac,2-[(2,6-dichlorophenyl)amino] benzeneacetic acid is an acidic compound (pKa 3.80 at 25 ℃) with very low aqueous solubility (6×10^-5 M at 25℃) in the unionised form, which is unsuitable for TDDS. In this study, we synthesized a series of new diclofenac acid (DA) -alkanolamines ( diethanolamine, triethanolamine, N-(2-hydroxyethyl) pyrrolidine) in order to increase the transdermal flux of diclofenac.DSC and FT-IR studies demonstrated that diclofenac with each alkanolmine had formed salts, and HPLC method was employed to determine the solubilities of DA and the values of partition coefficent(n-octyl alcohol/water) of them. Comparing with diclofenac, the salts have higher solubilities in water and appropriate partition coefficients for TDDS. In the study we evaluated the transdermal delivery potential of DA , diclofenac sodium and its three kinds of alkanolmine salts in vitro, the results indicated that diclofenac acid diethanolamine(DA-D) had the highest flux in the five compounds, so DA-D was employed as the compound to prepare patches. The effect of various classes of chemical enhancers were investigated for the transdermal delivery of the DA-D across rat skin in vitro, Azone in combination with menthol...