Profiling in vitro drug release from subcutaneous implants: a review of current status and potential implications on drug product development.
This review presents current methods and strategies for studying the release characteristics of drugs from subcutaneous implant dosage forms. Implants are dosage forms that are subcutaneously placed with the aid of surgery or a hypodermic needle, and are designed to release drugs over a prolonged period of time. In most cases, the objective of a release test is to identify sufficiently discriminatory procedures that in turn would provide data to set meaningful specifications. Additional information obtained from successful in vitro-in vivo correlations (IVIVC) and accelerated drug release tests are extremely useful during drug product development. Although several workers have employed different methods to monitor drug release from these dosage forms, the use of the compendial Apparatus 4 (flow-through) device has been recommended in a publication on FIP/AAPS Guidelines for drug release testing of modified release dosage forms. However, most of method development with this device has focused on oral immediate or controlled release dosage forms and little published information is available on implants. Two recent reports on workshops provide useful information on methods to evaluate drug release from controlled-release parenterals such as implants, including IVIVC and accelerated release testing. Details on such studies, however, are generally not found in the literature; possibly because of the high proprietary value of methodologies for establishing release specifications of implant dosage forms. This article reviews the current status of methodologies used in the investigation of drug release from subcutaneous implants with an emphasis on mechanistic, product development and regulatory perspectives.
Iyer
Sunil S
SS
Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298-0533, USA.
Barr
William H
WH
Karnes
H Thomas
HT
D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004343:Drug Implants / Q000008:administration & dosage / Q000378:metabolism*; D066298:In Vitro Techniques; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism; D040521:Subcutaneous Tissue / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods
D004343:Drug Implants; D004364:Pharmaceutical Preparations