Designing the formulations in circadian rhythm activity with chronotherapeutic drug delivery system using ramelteon

Abstract

Ramelteon is an orally sleep promoting agent that is chemically designated as (S)- N- [2-(1,6,7,8-Tetrahydro-2H-indeno-[5,4b] furan-8-yl) ethyl] propionamide and contains one chiral centre. Ramelteon is a neutral compound with no acid or base functional groups, and as such, its aqueous solubility is independent of pH. The activity of Ramelteon at the MT1and MT2 receptors is believed to contribute to its sleep-promoting properties, as these receptors, acted upon by endogenous melatonin, are thought to be involved in the maintenance of the circadian rhythm underlying the normal sleep-wake cycle. These maintenance of circadian rhythm can be well controlled by designing the formulations with chronotherapeutic drug delivery system. This article summarizes to design, develop and evaluate the chronotherapeutic drug delivery system with various approaches using control release polymers like Eudragit RSPO, Hydroxy propyl methyl cellulose (HPMC), Ethyl cellulose etc., the approaches like compression coating technique, pulsatile drug delivery system and coating technique. The main objective of controlling the drug release pattern is to achieve the lag time of 2 hours followed by drug release profile for 4 hours. Also an attempt has been made to conclude on various approaches studied which can be used in the treatment of circadian rhythm using Ramelteon API.