IMPLANTS

IMPLANTS Implants are long-acting dosage forms that provide continuous release of the drug substance often for periods of months to years. They are administered by the parenteral route and are sterile. Some implants approved as animal drugs to be administered subcutaneously to the ears are not required to be sterile. Typically for systemic delivery, they may be placed subcutaneously, or for local delivery, they can be placed in a specific region in the body (e.g., in the sinus, in an artery, in the eye, in the brain). Implants are usually administered by means of a suitable injector or by surgical procedure. Polymer implants can be formed as a single-shaped mass such as a cylinder. The polymer matrix must be biocompatible (see The Biocompatibility of Materials Used in Drug Containers, Medical Devices, and Implants), but it can be either bioabsorbable or nonbioabsorbable. Shaped polymer implants are administered by means of a suitable special injector. Release kinetics are typically not zero-order, but zero-order kinetics are possible. Drug substance release can be controlled by the diffusion of the drug substance from the bulk polymer matrix or by the properties of a rate-limiting polymeric membrane coating. Polymer implants are used to deliver potent small molecules like steroids (e.g., estradiol for cattle) and large molecules like peptides [e.g., luteinizing hormone-releasing hormone (LHRH)]. Example durations of drug substance release are 2 and 3 months for bioabsorbable implants and up to 3 years for nonbioabsorbable implants. An advantage of bioabsorbable implants is that they do not require removal after the release of all drug substance content. Nonbioabsorbable polymer implants can be removed before or after a drug substance release is complete or may be left in situ. An implant can have a tab with a hole in it to facilitate suturing it in place (e.g., for an intravitreal implant for local ocular delivery). Such implants may provide a therapeutic release for periods as long as 2.5 years. Drug substance-eluting stents combine the mechanical effect of the stent to maintain arterial patency with the prolonged pharmacologic effect of the incorporated drug substance (to reduce restenosis, inhibit clot formation, or combat infection). As an example, a metal stent can be coated with a nonbioabsorbable or bioabsorbable polymer-containing drug substance. The resultant coating is a polymeric matrix that controls the extended release of the drug substance. PREPARATION Cylindrical polymeric implants are commonly made by melt extrusion of a blend of drug substance and polymer, resulting in a rod that is cut into shorter lengths. Polymer implants also can be made by injection molding. Still, other implants are assembled from metal tubes and injection-molded plastic components. Sterility can be achieved by terminal sterilization or by employing aseptic manufacturing procedures.