Nanoemulsion technology for sublingual delivery of melatonine: characterization and preliminary data of absorption

Melatonin (5-methoxytryptamine) is a natural occurring molecule which exerts physiologic role of circadian sleep-wake cycle in humans. Melatonin is secreted from the pineal gland placed in the center of the brain, far from blood-brain barrier. Thanks to its ascertained safety in humans and low cost, melatonin is widely employed in the market of drugs and nutritional supplements mainly claiming its effectiveness in sleep-wake cycle regularization, anxiolytic and antioxidant activity. Over the last decades, melatonin bioavailability has been investigated in humans and animal models. Literature data pointed out a limited bioavailability of melatonin after oral intake, together with a high variability from subject to subject. This chapter describes, characterizes and preliminary assesses the effectiveness of a new nanoemulsified system for the sublingual administration of melatonin. The very small droplet size which characterizes this system, potentially allows melatonin to be delivered from a sublingual spray formulation which promotes its absorption through the lingual epithelium so reaching venous systemic circulation avoiding first liver passage through the portal circulation. It seems, in fact, that liver first passage express the main biochemical phenomena involved in the high clearance and relative low bioavailability of melatonin after oral assumption.