Probing Melatonin’s Release Pattern from Oral Solid Dosage Forms Using Synthetic Biopolymers

Melatonin (N-acetyl-5-methoxytryptamine) (MLT) is a naturally occurring hormone produced endogenously, primarily in the suprachiasmatic nucleus. MLT exhibits a plethora of uses particularly in the treatment of sleep disorders (sleep onset and maintenance). However, due to its short biological half-life, MLT cannot maintain effective plasma concentrations for a prolonged period when it is exogenously taken from immediate-release formulations. The present study aims at developing modified release systems capable of gradually releasing MLT, thereby sustaining its pharmacological effect over eight hours. To this end, modified-release tablets were prepared using new polymeric excipients based on polylactic acid (PLA). Both neat PLA and PLA copolymers with polyethylene glycols (PEGs) of varying molecular weights (PLLA-PEG-PLLA_4000, PLLA-PEG-PLLA_6000, and PLLA-PEG-PLLA_8000) were used, along with other excipients. Certain formulations delivered MLT comparatively fast and may therefore be useful for sleep onset problems, others matched the release behaviour of the marketed product Circadin®, and the rest released the hormone in a more prolonged manner.