Biodegradable,implantable sustained release systems based on glutamic acid copolymers

Polymer pellets that contain drugs and may be implanted under the skin offer effective means for providing sustained, controlled drug therapy to humans and animals. Among the most useful drug delivery systems are those based on biodegradable polymers that ultimately are absorbed by the body — eliminating the need for their surgical removal. Copolymers of L-glutamic acid and γ-ethyl L-glutamate biodegrade to L-glutamic acid and ethanol, at rates that are determined by the initial copolymer composition. The materials are permeable to a wide range of drugs, including steroids, narcotic antagonists, peptide hormones, antimalarials, and anticancer agents. When fabricated into matrix rods or capsules, the copolymers have been used to release drugs in animals at constant rates for prolonged periods of time. p]In this study, rods composed of a blend of drug and copolymer were found to be useful for the long-term release (i.e., 6 to 24 months) of drugs having low aqueous solubility, such as progesterone and levonorgestrel. Capsules, composed of a copolymer sheath surrounding the drug, were better suited for shorter durations of release (i.e., up to 6 months) of drugs having higher aqueous solubility, such as luteinizing hormone-releasing hormone and naltrexone. The physical dimensions and copolymer compositions of either dosage form were readily varied to meet specific delivery rate and duration objectives while satisfying equally important degradation requirements.