Melatonin mini-tablets and method of manufacturing the same
Inventors
Assignees
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Publication Number
US-10722494-B2
Publication Date
2020-07-28
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 disclosure addresses controlled-release melatonin mini-tablet formulations having a diameter less than or equal to 4 mm for pediatric, geriatric, and dysphagia patient populations, where larger tablets may present compliance issues. The mini-tablets are intended to induce sleep and to provide a release profile suited to oral ingestion by a human patient.
The invention defines quantitative performance and release behavior for the controlled-release mini-tablets, including a melatonin release of less than 50% within 1 hour and about greater than 70% within 6 hours after oral ingestion. It further describes minimal melatonin blood levels of about 60 to 200 pg/mL over at least four hours as a performance target, and characterizes the resulting melatonin exposure as substantially simulating a normal endogenous melatonin plasma profile.
The mini-tablet formulations contain 1 mg or 5 mg melatonin with one or more pharmaceutically acceptable carriers, and include ammonio methacrylate copolymer, calcium hydrogen phosphate dihydrate, and lactose monohydrate. A weight ratio between melatonin, ammonio methacrylate copolymer, calcium hydrogen phosphate dihydrate, and lactose monohydrate is defined in the range 1:1.1-5.9:0.8-8.3:1.8-8.8, with options for specific polymer types and for additional excipients and coatings.
Claims Coverage
The partial content provides two independent claims: one directed to a controlled-release melatonin mini-tablet with a defined diameter and in vivo release profile, and a second directed to a mini-tablet formulation designed to substantially simulate a normal endogenous melatonin plasma profile. Across these independent claims, the inventive coverage centers on the small mini-tablet size, the defined release/plasma-response performance, and the specified formulation components with a defined melatonin-to-excipient weight ratio.
Controlled-release melatonin mini-tablet with defined size and in vivo release profile
A controlled-release melatonin mini-tablet comprising 1 mg or 5 mg melatonin and one or more pharmaceutically acceptable carriers, wherein the mini-tablet has a diameter 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 a human patient.
Defined formulation composition with melatonin-to-excipient weight ratio
The mini-tablet contains ammonio methacrylate copolymer, calcium hydrogen phosphate dihydrate, 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.
Mini-tablet formulation substantially simulating normal endogenous melatonin plasma profile
A pharmaceutical mini-tablet formulation comprising 1 mg or 5 mg melatonin in combination with at least one pharmaceutical carrier, diluent or coating, wherein, upon administration to a patient, the mini-tablet formulation releases melatonin over time such that the patient's melatonin plasma profile substantially simulates the melatonin plasma profile of a human having a normal endogenous melatonin profile.
Taken together, the independent claims require a controlled-release melatonin mini-tablet of very small diameter with specified early and later melatonin release behavior, and a mini-tablet formulation that is designed so the patient melatonin plasma profile substantially simulates a normal endogenous profile. Both independent claims further require the same core formulation components—ammonio methacrylate copolymer, calcium hydrogen phosphate dihydrate, and lactose monohydrate—with a defined melatonin-to-component weight ratio.
Stated Advantages
Enables a melatonin release over time such that the patient's melatonin plasma profile substantially simulates the melatonin plasma profile of a human having a normal endogenous melatonin profile.
Provides a mini-tablet with a diameter less than or equal to 4 mm suitable for pediatric, geriatric, and dysphagia patient populations.
Induces sleep as described for the mini-tablets.
Documented Applications
Pediatric patients (2–18 years) and geriatric patients (>65 years) as described in the context of melatonin mini-tablet use for compliance and administration.
Dysphagia patient populations as described in connection with mini-tablet administration.
ASD and neurogenetic diseases in children, supported by a human clinical trial showing improvements versus placebo.
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