Background: N-Acetylserotonin (NAS, N-acetyl-5-hydroxytryptamine) is the immediate
precursor of the neurohormone melatonin (MT, N-acetyl-5-methoxytryptamine), which regulates
sleep and wake cycles. NAS is produced by the N-acetylation of serotonin and is converted to melatonin
via the action of Acetylserotonin O-methyltransferase (ASMT). Like melatonin, NAS acts as
an agonist on the melatonin receptors MT1, MT2, and MT3. However, as NAS is abundant in specific
brain areas, separate from serotonin and melatonin, it may also have discrete central effects.
Indicatively, it has been reported that NAS may play a role in the antidepressant effects of Selective
Serotonin Reuptake Inhibitors (SSRIs) and Monoamine Oxidase Inhibitors (MAOIs).
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Objective: To decipher the controlled release characteristics of the active substances (NAS and MT)
in a quick initial pace, aiming at a satisfactory sleep-onset related anti-depressive profile and prolonged
release, thereafter, targeting at coping with poor sleep quality problems.
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Methods: A series of hydrophilic matrix tablets involving as excipients, hydroxypropylmethylcellulose
(HPMC) K15M, low viscosity sodium alginate, lactose monohydrate, and polyvinylpyrrolidone (PVP)
M.W.: 10.000 and 55.000) was developed and tested at two dissolution media (pH 1.2 and 7.4).
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Results: The results showed that commonly used excipients with different physicochemical properties
govern the controlled release of NAS and MT from solid matrix systems.
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Conclusions: We have demonstrated how broadly used excipients affect the in vitro controlled
release of NAS and MT from solid pharmaceutical formulations. Currently, we extend our studies
on the controlled release of these drugs using various other biopolymers/formulants of different
physicochemical characteristics, which will help to highlight the discrete release profiles of NAS
and MT.
API – excipient interactions in non-biodegradable solid matrix systems
