Chronotherapy

The aim of present work was to develop pulsatile release dosage form for chronotherapy of hypertension. Considering the biopharmaceutical, pharmacodynamics reasons of Valsartan and circadian rhythm of hypertension a time controlled rupturable tablet, which allowed the release of Valsartan in time controlled release manner was developed for treating early in the morning surge of blood pressure. Core tablet for formulation were prepared using direct compression technique and evaluated for various parameters like % drug content, hardness, thickness, friability and In-vitro disintegration time. To get desired lag time and release profile to achieve pulsatile delivery tablets were coated with ethyl cellulose: Eudragit L100 (3:1), containing dibutyl phthalate and magnesium stearate. Coated tablet was evaluated for in vitro dissolution study, Drug content and rupture time. Optimization was done by using 32 full factorial design by using conc. of croscarmellose in core and coating level as independent variables and rupture time or lag time as dependent variable. Formulation F-5 was found to optimized formulation containing 5% of superdisintegrant in core tablet and 5 % coating level. From the study it is also concluded that Increase in coating level increases lag time & increase in concentration of superdisintegrant decreases lag time.

Chronotherapeutic drug delivery system is useful in the treatment of disease, in which drug availability is timed to match rhythm of disease, in order to optimize therapeutic effect and minimize side effects. There is an impact of circadian rhythms in the symptoms of certain diseases like asthma, arthritis, depression, ulcer, allergic rhinitis, sleep disorders etc. The human body follows the solar/ lunar adaptations known as biological clock. The role of circadian rhythms in the mechanisms of disease and the pharmacokinetics and pharmacodynamics of medications constitutes a challenge to drug-discovery and drug-delivery scientists. We must strive to develop intelligent drug-delivery systems that can affect a target cell or organ system at that circadian time when it is possible to optimize desired therapeutic outcomes and minimize or avert adverse effects. The present article covers findings about the effects of biorhythms on various disorders, and their implications for drug therapy are discussed. Here we also reviewed the design of novel chronopharmaceutical drug delivery systems that might be able to release the therapeutic agents at predetermined intervals. Keywords:Chronotherapy, Circadian rhythm, Chronopharmaceutics, Chronopharmacokinetics.