IMPLANTABLE CONTROLLED RELEASE DRUG DELIVERY SYSTEMS - A REVIEW

Origins of rate controlled implantable drug delivery dates back to 1964 when silicone implants were used to prolong a drug effect. Despite much activity in the years since 1964, the progress to a safe, effective and acceptable implant system(s) has been slow. The critical factors in implant research which need to be addressed include: erodibility, reproducibility, lack of irritation and carcinogenicity, lack of dose dumping, duration and pulses. While it is possible to surgically implant and remove drug-containing devices or polymeric matrices, the requirement for such intervention could have a significant negative impact on the acceptability of a product candidate. In recent years, two implant systems have been approved for human use; (a) a silicone-based device (Norplant(R)), and (b) a system based on lactide/glycolide copolymers to release a luteinizing hormone - releasing hormone (LHRH) agonist for treatment of male reproductive tract tumours. This approach to drug delivery is very appealing for a number of classes of drugs, particularly those that cannot be given via the oral route, and drug candidates whose therapeutic index is relatively large. This article reviews the background to implantable drug delivery systems, the rationale behind using implantable drug delivery systems, the types of systems being currently researched, and the various methods available for their evaluation.