Melatonin mini-tablets and method of manufacturing the same

A method of inducing sleep in a human in need thereof, the method comprising:

• orally administering a controlled-release mini-tablet to the human,
• wherein said controlled-release melatonin mini-tablet comprises 1 mg, 2 mg, 3 mg, 4 mg or 5 mg melatonin;
• and one or more pharmaceutically acceptable carriers,
• wherein the mini-tablet has a diameter of less than or equal to 4 mm and has a release profile of less than 50% melatonin release within 1 hour, and about greater than 70% melatonin release within 6 hours of oral ingestion by the human,
• wherein the mini-tablet contains ammonio methacrylate copolymer, calcium hydrogen phosphate dihydrate, lactose monohydrate, and
• wherein the ratio between melatonin, ammonio methacrylate copolymer, calcium hydrogen phosphate dihydrate and lactose monohydrate by weight is 1:1.1-5.9:0.8-8.3:1.8-8.8.

A method of inducing a phase shift of the circadian rhythm of a human in need thereof, the method comprising:

• orally administering a controlled-release mini-tablet to the human,
• wherein said controlled-release melatonin mini-tablet comprises 1 mg, 2 mg, 3 mg, 4 mg or 5 mg melatonin;
• and one or more pharmaceutically acceptable carriers,
• wherein the mini-tablet has a diameter of less than or equal to 4 mm and has a release profile of less than 50% melatonin release within 1 hour, and about greater than 70% melatonin release within 6 hours of oral ingestion by the human,
• wherein the mini-tablet contains ammonio methacrylate copolymer, calcium hydrogen phosphate dihydrate, lactose monohydrate, and
• wherein the ratio between melatonin, ammonia methacrylate copolymer, calcium hydrogen phosphate dihydrate and lactose monohydrate by weight is 1:1.1-5.9:0.8-8.3:1.8-8.8.

A method of safely inducing and maintaining sleep in a human in need thereof, the method comprising:

• providing a pharmaceutical product comprising one or more melatonin mini-tablets capable of inducing sleep in a patient and achieving a minimal blood level of about 60 to about 200 picograms melatonin per milliliter over at least four hours following the administration without inducing unacceptable side effects in the human, wherein said pharmaceutical product is manufactured by combining a therapeutically effective amount of melatonin and one or more pharmaceutically acceptable carriers to produce a mixture, compressing the mixture into one or more mini-tablets that each have a diameter of less than or equal to 4 mm such that the mini-tablet has a release profile of less than 50% melatonin release within 1 hour, and about greater than 70% melatonin release within 6 hours of oral ingestion by the human, and optionally filling a plurality of the mini-tablets into a capsule;
• and
• orally administering the one or more mini-tablets to the patient,
• wherein the mini-tablet contains 1 mg, 2 mg, 3 mg, 4 mg or 5 mg melatonin, and
• wherein the one or more mini-tablets contain ammonio methacrylate copolymer, calcium hydrogen phosphate dihydrate, lactose monohydrate, and wherein the ratio between melatonin, ammonio methacrylate copolymer, calcium hydrogen phosphate dihydrate and lactose monohydrate by weight is 1:1.1-5.9:0.8-8.3:1.8-8.8.