ABSTRACT

When considering new options for drug (small molecule, peptide, protein, etc.) 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 intraveneous or subcutaneous administration, the development of injectable dosage forms is more likely to succeed commercially than alternative routes of delivery (oral, topical, pulmonary), assuming that the injectable dosage forms provide the desired pharmacokinetics, efficacy, and safety. Injectable modified release systems are of particular importance due to their ability to alter the pharmacokinetics of the drug. This ability to control the systemic or local residence of a given protein may alter significantly the efficacy or safety of the compound. In the case where the active compound has a short half-life in vivo, a modified release system can extend exposure after a single administration (Table 1). This extended exposure could reduce significantly the number of doses a patient may be required to receive to control their condition. An added benefit of these types of systems is the ability to administer high doses per injection with a fairly low maximum serum concentration (Cmax). This avoids any undesired side effects or toxicity that may be associated with high Cmax values observed after direct injection of the drug

compound alone. The focus of this section is modified release systems that are injected or surgically placed in the body where they then deliver the loaded drug. The systems broadly represent four classes of modified release systems: implants, microspheres, injectable gels, and nanospheres (liposomes, nanocrystals). The section covers recent developments in the area of injectable or implantable sustained/controlled release systems including several biodegradable matrices suitable for modified delivery of drugs. In light of the ever-increasing number of products in clinical development which employ polymer conjugation to prolong circulation time in the body a chapter is also included on modification of drug release by chemical modification.