In vitro and in vivo long term release of apomorphine from polymer matrices

Since apomorphine actually reveals high efficacy in treatment of Parkinson' s disease but only has a very short half life, it is of only limited clinic al significance. To overcome this substantial disadvantage, drug applicatio n by long term delivery systems could be one possibility. Based on this bac kground, ethylene vinyl acetate polymeric delivery systems were manufacture d that differed in size, with either coated or uncoated surfaces, but were similar in apomorphine loading. Release from uncoated polymeric delivery sy stems followed first order kinetics, whereas coated polymeric delivery syst ems showed within the first 40 days a period of first order kinetics releas e, in which the release rate is approximately half that of the uncoated pol ymeric delivery systems, followed by a zero order kinetics release for more than 130 days with a daily release rate of 3.1 +/- 0.2 mg. In vivo release was investigated by determining plasma apomorphine concentrations after im planting polymeric delivery systems into the abdominal cavities of rats. An imals with uncoated polymeric delivery systems exhibited symptoms of an apo morphin overdosage within 20 days after surgery. Using coated polymeric del ivery systems, a steady state plasma concentration of 15 ng/ml was observed , which was maintained over a period of 130 days after an initial period of high plasma concentrations. Based on our results, it is concluded that pol ymeric delivery systems might be an appropriate method for applying apomorp hine for the treatment of Parkinson's disease.