0545 Bi-Layer Melatonin Tablet Provides Immediate and Extended Absorption to Address Primary Sleep Issues

Abstract

Abstract Introduction Melatonin is a naturally-occurring hormone that functions in the regulation of the sleep-wake cycle. Exogenous melatonin has demonstrated utility for the induction and maintenance of sleep. Modulation of tablet dissolution rates can be achieved by strategically using binding agents in two layers to rapidly raise melatonin levels and sustain elevated levels over time to better emulate normal nocturnal melatonin secretion. Methods A randomized, double-blind, controlled cross-over study was conducted in healthy adults (n=18) to investigate the pharmacokinetics of a 4.5 mg melatonin bi-layer tablet with either prolonged-release (PR) or immediate-release (IR) characteristics. Blood samples were collected at 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8 and 10 h post-ingestion and melatonin concentrations were quantified. Results The PR formulation had a lower maximum concentration (Cmax, p<0.002), but a longer time to reach maximum concentration (Tmax, p<0.001). Absorption rate constant (Ka) and terminal disposition rate constant (λ) were both lower in PR melatonin than the IR formulation (p<0.001), indicating slower absorption and elimination rates. These measures were consistent with significantly greater absorption (ta1/2, p<0.002) and elimination half-lives (t1/2, p<0.001) in the IR formulation compared to the PR formulation. Additionally, plasma melatonin concentrations reached pre-ingestion values by 8 h post-administration of the PR formulation, indicating that individuals sleeping for a recommended 7-9 hours will wake with normal melatonin levels, when taken an hour before bedtime. Conclusion Prolonged-release bi-layer melatonin tablet safely and effectively extends the absorption of exogenous melatonin compared to an immediate-release formulation. Support Pharmavite, LLC