Controlled release implant dosage forms for cardiac arrhythmias: Review and perspectives

Cardiac implants using drug-polymer systems for the release of anti-arrhythmic agents directly to the myocardium have been successfully utilized in experimental studies for preventing and treating arrhythmias. This approach is hypothesized to be optimal since anti-arrhythmic agents are provided directly to the heart, and therefore the possibility of systemic side effects is reduced. Furthermore, anti-arrhythmic agents with poor oral bioavailability or with first-pass clearance characteristics following intravenous administration, such as the class III agent ibutilide, are optimally used by the direct cardiac route of administration. Cardiac controlled release implants have been demonstrated to be effective for optimizing the therapy of ventricular tachycardia, ventricular fibrillation, and atrial flutter. Monolithic matrices have been used for fixed rate release kinetics, and modulation of release has been possible through the use of iontophoretic drug delivery systems. Future implants will interface with forefront strategies in tissue engineering and molecular genetics to provide optimal therapy of the diseased arrhythmogenic myocardium.