Development and evaluation of a novel pharmaceutical dose form for the induction of emesis in canines

Ingestion of toxic materials continues to be a problem with both humans and canines. Treatment procedures such as emesis have now fallen out of favor largely due to well designed studies in humans which have shown that they are ineffective therapeutically and probably provide no benefit in terms of patient outcome. In veterinary medicine emesis is still used therapeutically in dogs as emesis is somewhat more useful in this species due to differences between human and canine intoxications primarily in terms of the nature of the intoxicant and the quantity consumed. For induction of emesis in dogs, apomorphine is the most appropriate drug but it is generally not used since it has a range of potentially serious dose-related adverse-effects, wide patient variability in terms of response and at present can only be administered by injection. Since the drug can be absorbed by the ocular route, a controlled-release product in the form of an ocular insert was designed, developed and tested. After placement in the eye, apomorphine would be released in a controlled fashion and absorption would occur until emesis is achieved. Further drug absorption would be stopped by removal of the insert so the minimal amount of drug required for emesis would be administered and the occurrence of dose-related adverse effects may be avoided or reduced. In this project, a suitable insert was designed, a method of fabrication developed and the mechanism of release and shelf-life of the product determined. In a clinical trial the insert was shown to induce emesis with an efficacy similar to intravenously administered apomorphine but with a much lower incidence of adverse effects. Although the insert performed well clinically there were some short-comings with the product and several suggestions regarding product improvement are presented.