Melatonin tablet and methods of preparation and use

Abstract

The present invention provides a pharmaceutical composition for sublingual or buccal administration of actives with low to poor aqueous solubility, e.g. the indole hormone melatonin, which contains a solution of the active in a pharmaceutically acceptable solvent adsorbed or absorbed onto particles of a pharmaceutically acceptable carrier and methods of preparing and using the pharmaceutical composition.

Description

[0001]This application claims priority from U.S. Provisional Patent Application No. 60 / 922,921, filed on Apr. 11, 2007, through PCT Application No. PCT / US2008 / 004615 filed on Apr. 10, 2008, the disclosures of which are hereby incorporated by reference in their entireties.BACKGROUND OF THE INVENTION[0002]Hormones such as the indole hormone, melatonin, are widely distributed in both plant and animal sources. Melatonin can be found in human milk, bananas, beets, cucumbers, and tomatoes. Chemically, melatonin is N-acetyl-5-methoxytryptamine, a derivative of serotonin, which in turn is derived from tryptophan. Melatonin is a ubiquitous natural neurotransmitter-like compound produced primarily by the pineal gland, and is involved in numerous aspects of the biological and physiologic regulation of body functions.[0003]See, e.g., Malhotra, S., et al., Medscape General Medicine 2004; 6(2), 46; and www.nlm.nih.gov / medlineplus / print / druginfo / natural / patient-melatonin.html for general discussio...

AI Technical Summary

Benefits of technology

[0018]The composition of the subject invention advantageously provides the active ingredient, e.g., a hormone such as melatonin having relatively low to poor solubility in aqueous solvents, in a dissolved form. Being in a dissolved form, the melatonin can be directly absorbed into the bloodstream through the oral mucosa, without having to be dissolved by the aqueous environment provided by saliva in the mouth or in the gastrointestinal tract. A further advantage of the drug delivery system of the subject invention includes enhanced oral mucosal absorption of the active provided in the composition because less drug is swallowed as undissolved drug released from the dosage form. Accordingly, this drug delivery system provides for rapid onset of drug action with higher and more consistent bioavailability.

Problems solved by technology

However, as with most oral preparations, it can take more than 30 minutes after administration for the blood plasma concentration of melatonin to reach its peak.

Further, melatonin's oral bioavailability is poor and erratic.

Thus, oral administration of melatonin in currently available preparations does not provide for rapid onset of action, and its poor and erratic GI absorption make it an unsuitable route of administration.

Due to melatonin's poor water solubility much of the dosage from a currently available preparation is swallowed undissolved in the saliva, leading to poor and erratic absorption in the GI tract.

Accordingly, hormone drugs such as melatonin having low to poor water solubility, are expected to be poorly suited for buccal or sublingual administration.

However, sprays are less desirable because of inherent compliance issues such as improper manipulation of the actuator, swallowing of the dosage before dissolution of the drug, and the restrictions on usage when the patient has sinus congestion or a head cold.

This again leads to erratic and poor melatonin bioavailability.

Therefore sprays are not the optimal route for routine melatonin administration.

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