Thesis (M.Sc. in Pharm.)--Chulalongkorn University, 1996

A membrane-controlled transdermal drug delivery system was developed for sustained-release of diclofenac diethylamine. The effect of various solvents such as benzyl alcohol, N.N-dimethyl acetamide, ethyl alcohol, isopropyl alcohol, propylene glycol, and polyethylene glycol 400 on drug stability were studied, propylene glycol exhibited higher stability and suitability than other solvents. The effect of pH values of phosphate buffer solutions on drug stability were investigated, it was found that at pH value of 7 showed higher stability than others. The effect of various polymers, such as poloxamer F-127, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, and sodium alginate, on drug stability were, also, investigated. It was revealed that the drug stability in poloxamer F-127 and hydroxypropyl methylcellulose were higher than others. The formulations contained propylene glycol and pH 7 phosphate buffer were assessed by the in-vitro release of drug through microporous polyethylene film using modified Keshary-Chien diffusion cell. It was found that increasing drug concentration will increase the release rate while the correlation of the gelling agent concentrations and the release rate is the opposite for all polymers. The formulations which produced equivalent release rate to Voltaren(r) emulgel fill in patch (VEP) were studied for the in-vitro skin permeation, using shed snake skin (Elaphe obsoleta). They showed the zero order kinetics. Formulations of diclofenac diethylamine patch which contained 10% poloxamer F-127 and produced equal permeation rate to VEP was suitable to employ in in-vivo study using carrageenan-induced paw edema in Wistar rat, compared with topical administration commercially available of Voltaren(r) emulgel. It was indicated that the drug can be released from the patch into the rat dorsal skin and found to be more effective than the marketed gel for upto 12 hours. It can be summarize that a membrane-controlled type transdermal diclofenac diethylamine delivery system could be developed using 10% poloxamer F-127 as a gelling agent and 14% propylene glgcol as a co-solvent.