A Timely Review of State-of-the-Art Chronopharmaceuticals Synchronized with Biological Rhythms

Extensive research into circadian rhythms and their influence on biological systems has given rise to the science of chronobiology and subsequently chronotherapy, the science of delivering drugs in synchrony with biological rhythms. The field of chronotherapeutics paves the way for advances and complexities in current drug delivery technology. The ultimate goal of current chronopharmaceutical research strives to design ideal chronotherapeutic drug delivery systems that respond to such therapeutic needs. Considering the fact that physiological events such as heart rate, blood pressure, plasma concentration of hormones, plasma proteins and enzymes display constancy over time, drug delivery systems with constant release profiles have thus been favored. However, due to circadian rhythms, the conventional paradigm of constant drug delivery may not be what is needed. Instead, precisely timed drug delivery systems are required in order to correlate drug delivery with circadian rhythms to provide maximum therapeutic efficacy for chronotherapeutic diseases when most needed. The aim of this review paper is to outline the concepts in designing chronopharmaceuticals from a clinical viewpoint of major chronotherapeutic diseases such as asthma, allergic rhinitis, cardiovascular disorders, rheumatoid arthritis and cancer as well as relatively minor niche areas of interest such as in glaucoma, diabetes, immunity, pain, gastric ulcers, epilepsy and even HIV/AIDS that would require chronotherapy. In addition this review paper attempts to concisely assimilate and explicate the role of circadian rhythms in these various disease states and provide a focused overview of the current state-of-the-art in designing strategies for chronopharmaceutical formulations employed for treating chronotherapeutic diseases. Keywords: Chronotherapeutic diseases, circadian rhythms, chronopharmaceuticals, emerging technologies, polymers, rate modulated drug delivery