Summary:
The pineal hormone melatonin (N-acetyl-5-methoxytryptamine), is an important
component in the regulation of circadian rhythms. The secretion of melatonin in
humans, performed in a photoperiodic way, is closely synchronized with the
habitual hours of sleep in humans. Human studies have also indicated that
increasing serum melatonin concentrations can trigger the onset of sleep.
However, the dosage forms of melatonin, which mimic the physiologically
secreted melatonin concentration versus time model, are limited.
In the context of this work, extensive studies were carried out concerning the
comparison of the physicochemical characteristics of different formulations and
mainly the pace of release of melatonin from these forms. Initially,
hydrophilic matrix tablets were prepared and tested with respect to their
ability to release melatonin in a quick initial pace, for treating sleep onset
problems. Conversely, other forms were designed to promote the release of
melatonin at a relatively slow initial pace, aiming at improving sleep quality
and/or sleep maintenance. In order to achieve the above objectives, matrix
tablets with excipients, like lactose, sodium alginate, hydroxypropyl
methylcellulose (HPMC K15M), dextran, Avicel PH 102 and PVP, were prepared. The
dissolution studies were conducted in two aqueous media (pH 1.2 and pH 7.4).
Moreover, the release of melatonin from coated tablets and from bi-layer, was
also studied. Finally, the encapsulation of melatonin in liposomes, their
physicochemical characteristics and the release profile of melatonin from them,
was investigated.
In conclusion, the results of the melatonin release showed that the presence of
dextran in the tablets, reduced the release of the active compound at an early
stage. The presence of lactose monohydrate led to slow release of the active
substance in acidic pH, while at pH 7.4, its presence causes acceleration of
the release of melatonin. The initial release rates of coated tablets were
decreased, in comparison with the rates of uncoated tablets, and the bi-layer
tablets showed quick initial release and relatively slow pace toward the end of
the experiment. The encapsulation of melatonin into liposomes and its
subsequent release, were found to converge to the targets of the present
project.
Keywords:
Melatonin, Release, Tablets, Nanotechnology, Liposomes
