Melatonin mini-tablets and method of manufacturing the same
Inventors
Assignees
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Publication Number
US-10869857-B2
Publication Date
2020-12-22
Expiration Date
Abstract
The instant invention is generally directed to a patient-friendly drug delivery system for targeted populations, such as pediatric and geriatric patients. Specifically, the present invention relates to a pharmaceutical composition in the form of mini-tablets. Even more specifically, the present invention relates to a pharmaceutical composition comprising a therapeutically-effective amount of melatonin in the form of mini-tablets.
Core Innovation
The invention relates to melatonin mini-tablets for patients who have difficulty swallowing tablets or capsules, including pediatric and geriatric patients. The mini-tablets have a diameter of less than or equal to 4 mm and are designed to provide a controlled-release profile, characterized by less than 50% melatonin released within 1 hour of dissolution and about greater than 70% melatonin released within 6 hours of dissolution.
The mini-tablets contain melatonin in doses of 1 mg, 2 mg, 3 mg, 4 mg, or 5 mg, and include pharmaceutically acceptable carriers. The carriers comprise ammonio methacrylate copolymer, calcium hydrogen phosphate dihydrate, and lactose monohydrate, and 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.
The invention further describes manufacturing a controlled-release melatonin mini-tablet by combining melatonin with one or more pharmaceutically acceptable carriers to produce a mixture and compressing the mixture into a mini-tablet. Controlled-release is achieved with the specified mini-tablet diameter and release profile, and the mixture may be prepared by direct compression and/or dry blending, with an optional coating and optional filling into a capsule.
Claims Coverage
The independent claims cover four distinct methods and one composition-based formulation, all grounded on the same controlled-release melatonin mini-tablet definition. Across these independent claims, the inventive features include specific mini-tablet size and controlled-release performance, specific melatonin dose options, specific carrier composition with defined weight ratios, and a safe-inducing claim with defined blood-level criteria.
Compressing to form a controlled-release mini-tablet for a specified release profile
Combining melatonin and one or more pharmaceutically acceptable carriers to produce a mixture and compressing the mixture into a mini-tablet having a diameter of less than or equal to 4 mm such that the mini-tablet has a controlled-release profile of less than 50% melatonin released within 1 hour of dissolution, and about greater than 70% melatonin released within 6 hours of dissolution.
Mini-tablet composition with ammonio methacrylate copolymer, calcium hydrogen phosphate dihydrate, and lactose monohydrate in a defined weight ratio
The controlled-release mini-tablet contains calcium hydrogen phosphate dihydrate, ammonio methacrylate copolymer, and lactose monohydrate, 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.
Inducing sleep by orally administering a controlled-release melatonin mini-tablet with defined size and release profile
Orally administering a controlled-release mini-tablet to the human, 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.
Inducing sleep safely by achieving a minimal blood melatonin level over at least four hours without unacceptable side effects
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.
Inducing a phase shift of the circadian rhythm using orally administered controlled-release mini-tablets
Orally administering a controlled-release mini-tablet to the human, 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.
Across the independent claims, the coverage centers on controlled-release melatonin mini-tablets with a diameter of less than or equal to 4 mm, a specified release profile, and defined melatonin dose options. The claims further require a specific carrier set with a defined weight ratio, while the safe-induction claim additionally requires achieving a minimal blood melatonin level of about 60 to about 200 picograms per milliliter over at least four hours without unacceptable side effects.
Stated Advantages
Inducing sleep in a human without unacceptable side effects while achieving a minimal blood melatonin level of about 60 to about 200 picograms per milliliter over at least four hours.
Improved sleep-related outcomes in children with autism spectrum disorder and/or neurogenetic diseases in a human clinical trial, including improved total sleep time and sleep initiation versus placebo after 3 months.
Documented Applications
Use of orally administered controlled-release melatonin mini-tablets to induce sleep in a human in need thereof, including for humans with difficulty swallowing tablets or capsules.
Use of orally administered controlled-release melatonin mini-tablets to induce a phase shift of the circadian rhythm of a human in need thereof.
Use in a human clinical trial in children with autism spectrum disorder and/or neurogenetic diseases, with outcomes reported after 3 months compared to placebo.
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