ABSTRACT
When considering new options for drug delivery, the most direct approach is usually parenteral administration. Because many in vivo preclinical research studies and early clinical trials are performed by direct injection, such as intravenous (IV), intramuscular (IM), or subcutaneous (SC) administration, the development of injectable controlled-release dosage forms is more likely to succeed commercially than alternative routes of delivery (oral, topical, pulmonary), assuming that these dosage forms provide the desired efficacy and safety [1]. The ability of controlled-release dosage forms to modulate the systemic or local persistence of a given drug may significantly alter the efficacy or safety of the drug compound. In the case where the active compound has a short half-life in vivo, a modifiedrelease system can extend exposure after a single administration (Table 1). By extending the drug exposure time, these systems significantly reduce the number of injections a patient must receive to control his condition. Another potential benefit of these types of systems is the ability to administer high doses of drug per injection with a lower maximum serum concentration (Cmax) than a bolus injection. In some cases, the Cmax from the controlled-release preparation may be lower than that achieved with the more frequent bolus drug administration typically used for treatment, thus avoiding any undesired side effects that may be associated with a high Cmax. In this section, we will discuss examples of modifiedrelease systems that are injected or implanted in the body where they then deliver a controlled release of the drug. Four classes of modified-release systems are reviewed: implants, microspheres, injectable gels, and nanospheres (liposomes). *Current affiliation: Targesome, Inc., Palo Alto, California, U.S.A.
