Therapeutic applications of implantable drug delivery systems

Abstract

In the past, drugs were frequently administered orally, as liquids or in powder forms. To avoid problems incurred through the utilization of the oral route of drug administration, new dosage forms containing the drug(s) were introduced. As time progressed, there was a need for delivery systems that could maintain a steady release of drug to the specific site of action. Therefore, drug delivery systems were developed to optimize the therapeutic properties of drug products and render them more safe, effective, and reliable. Implantable drug delivery systems (IDDS) are an example of such systems available for therapeutic use. The application of currently available implantable drug delivery systems is the main focus of this review. IDDS can be classified into three major categories: biodegradable or nonbiodegradable implants, implantable pump systems, and the newest atypical class of implants. Biodegradable and nonbiodegradable implants are available as monolithic systems or reservoir systems. The release kinetics of drugs from such systems depend on both the solubility and diffusion coefficient of the drug in the polymer, the drug load, as well as the in vivo degradation rate of the polymer, especially, in the case of the biodegradable systems. Controlled release of drug from the implantable pump is generally achieved utilizing the microtechnology of electronic systems and remote-controlled flow rate manipulation through the maintenance of a constant pressure difference. The third atypical class includes those which have been recently developed such as ceramic hydroxyapatite antibiotic systems used in the treatment of bone infections, intraocular implants for the treatment of glaucoma, and transurethral implants utilized in the treatment of impotence. The major advantages of these systems include targeted local delivery of drugs at a constant rate, less drug required to treat the disease state, minimization of possible side effects, and enhanced efficacy of treatment. Also, these forms of delivery systems are capable of protecting drugs which are unstable in vivo and that would normally require a frequent dosing intervals. Due to the development of such sustained release formulations, it is now possible to administer unstable drugs once a week to once a year that in the past required frequent daily dosing. Preliminary studies using these systems have shown superior effectiveness over conventional methods of treatment. However, one limitation of these newly developed drug delivery systems is the fact that their cost-to-benefit ratio (cost/benefit) is too high which restricts their use over conventional dosage forms. Hopefully, in the future, new implantable systems can be developed at a lower cost, thereby minimizing the cost-to-benefit ratio and therefore, be used extensively in standard therapeutic practice. Some of the most recently discovered implants are in the early developmental stages and more rigorous clinical testing is required prior to their use in standard practice.