Zero-order drug delivery: State of the art and future prospects

Pharmaceutical drugs are an important part of the global healthcare system, with some estimates suggesting over 50% of the world's population takes at least one medication per day. Most drugs are delivered as immediate-release formulations that lead to a rapid increase in systemic drug concentration. Although these formulations have historically played an important role, they can be limited by poor patient compliance, adverse side effects, low bioavailability, or undesirable pharmacokinetics. Drug delivery systems featuring first-order release kinetics have been able to improve pharmacokinetics but are not ideal for drugs with short biological half-lives or small therapeutic windows. Zero-order drug delivery systems have the potential to overcome the issues facing immediate-release and first-order systems by releasing drug at a constant rate, thereby maintaining drug concentrations within the therapeutic window for an extended period of time. This release profile can be used to limit adverse side effects, reduce dosing frequency, and potentially improve patient compliance. This review covers strategies being employed to attain zero-order release or alter traditionally first-order release kinetics to achieve more consistent release before discussing opportunities for improving device performance based on emerging materials and fabrication methods.