Drug delivery systems. 4. Implants in drug delivery

In comparison with many of the other drug delivery systems, implantable pumps and implants for variable rate delivery are at a crude stage of development. Although exceptions exist, the typical implantable pump consists of an electromechanically complex mechanism to regulate drug delivery from a percutaneous refillable reservoir, while power to drive the system comes from a transcutaneous energy transmission system. The potential for electrical or mechanical failure is high, and the systems are not yet sufficiently convenient or easy to use to recommend in a routine therapy. Problems with refilling of an apparently well designed implanted reservoir have been observed while, at the same time, cutaneous energy transmission systems are not well established. In most instances, the development of an elementary osmotic pump system dosage form follows a well defined path of physical-chemical formulation and clinical testing. The benefits most often provided by the dosage form are expected to be (1) increase in selectivity of drug action achieved by the system's zero-order release rate, and (2) decrease in frequency of administration. The success in achieving these values is quantifiable from the pharmacology of the drug substance and its pharmacokinetics. Osmotic and other technical approaches to producing economical, rate-controlled dosage forms will make it possible for all new pharmaecutical products to carry kinetic specification of rate as well as static specification of content. This review considers the characteristics of the ideal implantable pump, the clinical situations which require pumps, the limitations of portable pumps, and the detailed characteristics of existing implantable pumps and implants. Most of the review, however, focuses on insulin delivery because of the importance of this subject.