Chronotherapeutics and Chronotherapeutic Drug Delivery Systems

Chronotherapeutics refers to a treatment method in which in vivo drug availability is timed to match rhythms of disease, in order to optimise therapeutic outcomes and minimise side effects. It is based on the observation that there is an interdependent relationship between peak-to-trough rhythmic activity in disease symptoms and risk factors, pharmacologic sensitivity, and pharmacokinetics of many drugs. The specific time that patients take their medication is very important as it has significant impact on treatment success. Optimal clinical outcome cannot be achieved if drug plasma concentrations are constant. If symptoms of a disease display circadian variation, drug release should also vary over time. Drug pharmacokinetics can also be time-dependent; therefore, variations both in a disease state and in drug plasma concentration need to be taken into consideration in developing drug delivery systems intended for the treatment of disease with adequate dose at appropriate time. Various technologies such as time-controlled, pulsed, triggered and programmed drug delivery devices have been developed and extensively studied in recent years for chronopharmaceutical drug delivery. These, as well as pertinent issues, are addressed in this review.