In-vitro dissolution methods for controlled release parenterals and their applicability to drug-eluting stent testing

Abstract

Dissolution testing is a powerful tool for the characterization of dosage form performance in vitro under standardized conditions. In spite of the increasing number of parenterally administered medicinal products, currently there are no compendial dissolution test methods designed especially for these types of dosage forms. In addition to classical drug delivery systems, drug/device combination products, such as drug-eluting stents, are being used increasingly. This review describes the current methods that are used most often for in-vitro dissolution testing of parenteral dosage forms, i.e. the 'sample and separate' methods, the 'dialysis' methods, and the 'flow-through' methods, with a special emphasis on whether these methods can be used for drug-eluting stent testing. In the light of current regulatory requirements and with the exploding costs of preclinical and clinical development, test systems that include biorelevant parameters and are predictive of in-vivo performance are increasingly important. Published attempts to take biorelevant conditions into consideration in the design of dissolution test apparatus developed for parenteral dosage forms, including a method that was designed to emulate the embedding and flow-conditions at the site of stent implantation, have been outlined in this review. In spite of the large quantity of highly potent controlled release parenteral products marketed today, there is still a lack of suitable methods for in vitro dissolution testing for these dosage forms especially with regard to biorelevant testing conditions. For dosage forms implanted into tissues it seems of major importance to reproduce the transport forces which are predominant in vivo (diffusive versus convective) in the in-vitro experimental setup.