Controlled Release Melatonin Formulations

**81**

**1. Introduction**

**Chapter 5**

Approach

**Abstract**

*Per Os* Administered

Modified-Release Solid

A Review of the Latest

*Angeliki Siamidi and Yannis Dotsikas*

disorders, referring either to its onset or maintenance.

dosage forms, *per os* administration, experimental design

Formulations of Melatonin:

Developments Including the

Design of Experiments (DoE)

The pineal hormone melatonin (MLT) is a derivative of the amino acid *L*-tryptophan and controls the circadian diurnal rhythm and the seasonal biorhythm. Exogenous administration is aimed at alleviating sleep-related dysfunctions and jet lag, as it decreases sleep-onset latency, increases total sleep time and improves overall sleep quality. Besides these indications, MLT has been shown to have other actions, such as antioxidant, immune enhancement and anticancer. It has also been shown to be useful against cardiovascular, neurological and psychiatric diseases. In the context of this work, a review of the related literature on the modified release of MLT from its *per os* administered formulations is presented, including the utilization of the design of experiments (DoE) for the selection of the optimal composition of melatonin formulations. The chapter offers an account of the recent advantages on MLT's solid dosage forms suitable for treating sleep

**Keywords:** melatonin, circadian rhythm, sleep disorders, modified release, oral solid

Melatonin (MLT) is an indole amide hormone produced by the pineal gland, especially at night time and is mainly involved in the regulation of circadian and circannual rhythms. For clinical purposes (including Alzheimer's disease, insomnia, stroke, depression, Parkinson's disease, migraine, headache, etc.), exogenous MLT could be administered for alleviation of the symptoms. Irrespective of the pathological case, MLT's exogenous administration should mimic the typical nocturnal endogenous MLT levels. The release profile of these drug delivery systems should be in a controlled manner, due to MLT's short half-life of elimination and low bioavailability.
