Circadian rhythms and the role of time-delayed controlled release systems

Today's guest post come from Dr Vivekanand Bhardwaj.

The effects of circadian rhythms on the body are quite fascinating, and are yet to be fully incorporated into dosage form design. Conventional extended release systems can be applied to many conditions where symptoms exhibit a circadian pattern. However, they may also deliver drug when the patient doesn’t need it. This presents an opportunity for the development of more sophisticated, reliable chronopharmaceuticals, which are synchronised with the appearance of these symptoms.

What exactly are circadian rhythms and how do they affect therapeutic needs?

Derived from the Latin circa (‘around’) and dies (‘day’), the term “circadian cycle” refers to a 24 hour rhythmical activity cycle exhibited by many organisms. It explains why certain tasks are more difficult during the afternoon, when you may not be feeling at your most alert. But there are also much wider implications, particularly in the occurrence of disease symptoms. For example, congestive heart failure and asthma symptoms worsen during the night, sudden cardiac death, rheumatoid pain and cold and flu symptoms are all more prevalent in the early hours of the morning, while stomach acid and cholesterol production tend to increase in the evening.1,2

How can pharmaceuticals be designed to address this?

To address this requires the development of reliable time-delayed systems, capable of delivering the drug only when patients need it, for example during the night when they are asleep. The system should allow for variable release profiles (e.g. single pulsed release or multiple pulses with controllable time lags), yet should be practical, commercially viable and scalable for mass manufacture.

Drug Delivery International (DDi) has developed formulations that meet these requirements in several therapeutic areas. These time-delayed tablets employ a unique method to prevent drug release for a pre-determined duration after administration. In one example, if taken before bed, this would prevent reawakening for those who suffer from sleep maintenance insomnia. Another example is a pain relief system which delivers two pulses of drug, one immediately post-dose, and one when the patient is likely to be waking up the next morning, potentially allowing those who suffer from pain and stiffness related to rheumatoid arthritis to get to sleep and wake up pain free as well. The pulsed release properties of these formulations have been demonstrated in clinical studies.

This technology can be used to incorporate almost any drug type, and as the effects of circadian rhythms become more widely appreciated, such time-delayed solutions will become necessities in optimising therapy for patients.

For further information on the design and development of time-delayed formulations, visit www.drugdeliveryinternational.com


1. Smolensky and Peppas, Advanced Drug Delivery Reviews 59 (2007) 828–851.
2. Smolensky, Lemmer and Reinberg, Advanced Drug Delivery Reviews 59 (2007) 852–882.