Supervisors info:
Επικ. Καθηγήτρια Μαριλένα Βλάχου (επιβλέπουσα), Καθηγητής Ανδρέας Τσοτίνης, Αναπλ. Καθηγητής Κωνσταντίνος Δεμέτζος
Summary:
The pineal hormone melatonin (N-acetyl 5-methoxytryptamine), is an important
component in the regulation of seasonal and circadian rhythms. Its action is
believed to be mediated through a family of specific, high-affinity,
G-protein-coupled cell membrane receptors, and radioligand binding studies
using 2-[125I]-iodomelatonin have revealed a widespread, heterogeneous
distribution of binding sites throughout the central nervous system.
The secretion of the hormone is closely synchronized with the habitual hours of
sleep in humans. Ingestion of melatonin affects sleep propensity, duration and
quality of sleep, and has hypnotic effects. Human studies have also indicated
that increasing serum melatonin concentrations can trigger the onset of sleep.
However, the use of melatonin as a drug is hampered by its short biological
half-life and poor bioavailability. As a result, dosage forms, which mimic the
physiologically secreted melatonin concentration versus time model, are
limited.
In the context of this work a series of hydrophilic matrix tablets was prepared
and tested with respect to the ability of some of them to release melatonin in
a quick initial pace, for treating sleep onset problems, and of others to
release melatonin at a relatively slow initial pace, aiming at improving sleep
quality and/or sleep maintenance. In both cases it was indented to achieve
completion of the hormone’s release within eight hours. In order to achieve
quick initial release of melatonin, excipients like lactose, sodium alginate,
hydroxypropylmethylcellulose (HPMC K15 M), dextran and Avicel PH 102 were
employed in various combinations. Conversely, in order to effect slow initial
release of melatonin, tablets containing polyvinylpyrrolidone (PVP) of two
different molecular weights (10000 and 55000), and lactose monohydrate, were
prepared. The dissolution studies were conducted in two media of pH 1.2
(gastric simulated fluid) and pH 7.4 (intestine simulated fluid). In summary,
the results of the melatonin release from the above tablets showed that the
presence of lactose facilitates quick initial release, irrespectively of the pH
of the medium used. Moreover, when lactose was combined with Avicel PH 102 a
zero-order release mechanism, was attained. The presence of dextran in the
tablets reduced the release of the active compound at an early stage and an
anomalous diffusion release mechanism, was prevalent. The addition of PVP to
the tablets, regardless of its molecular weight, led to an initially slow and
then sudden release in the neutral medium, while in the acidic environment an
initial delay in the release of melatonin was followed by a more abrupt and yet
gradual release.
Keywords:
Melatonin, Hydrophillic matrices, Controlled release, Polyvinylpyrrolidone, Lactose monohydrate
