Abstract

When consuming pharmaceuticals or supplements, the pharmacokinetic parameters like bioavailability, maximum concentration and onset of action are of uttermost interest. This is especially true when it comes to the pineal gland hormone melatonin being involved in the sleep-wake cycle and is therefore applied to alleviate sleep disturbances. To reach the sleeping state quickly, high bioavailability combined with fast onset of action is needed. Herein, we present the development of a non-irritating nanoemulsion with a droplet size smaller than 60 nm for sublingual use. Scalability of the production process for commercial use was achieved. Furthermore, the pharmacokinetic parameters of the formulation were compared with a standard oral tablet of melatonin (both with a dose of 5 mg melatonin) in an open label, balanced, randomized, single-dose, two-treatment, two-sequence, two-period, two-way crossover study (n = 12). Comparing the pharmacokinetic parameters of the oral tablet and the spray formulation, the sublingual nanoemulsion leads to the highest bioavailability and up to two times faster onset of action in all cases. Clinical study number: SLS-CT-0003-22-MELA.

Keywords: Melatonin, Nanoemulsion, Bioavailability, Sublingual, Fast onset, First-passeffect, In human, Area under the curve, Lipid-based drug delivery system