Lactic/glycolic acid polymers as narcotic antagonist delivery systems.

Lactic/glycolic acid polymers of several compositions were evaluated as the vehicle material for long term, controlled delivery of narcotic antagonists. L(+)-lactic, and glycolic acids-designated L(+), and G, respectively-were converted to polymers with weight ratios of 75 L(+)/25 G, 90 L(+)/10 G, and 100 L(+). Naltrexone base and naltrexone pamoate were incorporated into these polymers as a physical blend at several drug/polymer mass ratios. The mixtures were formed into small cylinders and spheres which were suitable for subcutaneous implantation by means of a trochar. $\text{In vitro}$ screening was carried out followed by $\text{in vivo}$ testing in mice. Radioactive assay and direct challenge with morphine using the tail-flick test were used to evaluate the drug release. The release rates approximated zero-order kinetics for most of the release period and the narcotic antagonist response to a challenge dose of morphine was maintained from one month to over six months depending on the formulation tested. Factors affecting narcotic antagonist delivery system design were polymer composition, narcotic antagonist solubility, drug loading level of the dosage form, use of a pure polymer coating around the drug/polymer matrix, and the surface area/unit volume of the dosage form.