Controlled release dosage forms for high dose, water soluble and hygroscopic drug substances
Inventors
Allphin, Clark • Pfeiffer, James
Assignees
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Publication Number
US-10959956-B2
Publication Date
2021-03-30
Expiration Date
Abstract
Controlled release dosage forms are described herein. The controlled release formulations described herein provide prolonged delivery of high dose drugs that are highly water soluble and highly hygroscopic. In specific embodiments, controlled release dosage forms for delivery of a drug selected from GHB and pharmaceutically acceptable salts, hydrates, tautomers, solvates and complexes of GHB. The controlled release dosage forms described herein may incorporate both controlled release and immediate release formulations in a single unit dosage form.
Core Innovation
The invention relates to a method for treating cataplexy or excessive daytime sleepiness associated with narcolepsy by delivering a formulation comprising immediate release and sustained release portions. Both portions comprise at least one pharmaceutically active ingredient selected from gamma-hydroxybutyrate and pharmaceutically acceptable salts of gamma-hydroxybutyrate.
The sustained release portion comprises a core and a functional coating deposited over the core. The functional coating comprises one or more methacrylic acid-methyl methacrylate co-polymers present from about 20% to about 50% by weight of the functional coating, and the sustained release portion releases greater than about 40% of gamma-hydroxybutyrate by about 4 to about 6 hours.
The formulation is further defined by dissolution performance thresholds, including that the formulation releases at least about 30% of its gamma-hydroxybutyrate by one hour and releases greater than about 90% by 8 hours under defined dissolution apparatus conditions. The immediate release portion comprises about 75% and about 98% by weight of gamma-hydroxybutyrate and pharmaceutically acceptable salts, with the amount of gamma-hydroxybutyrate in the immediate release portion about 10% to 50% by weight of the total gamma-hydroxybutyrate in the formulation.
Claims Coverage
Independent claims are directed to methods of treating cataplexy or excessive daytime sleepiness associated with narcolepsy using gamma-hydroxybutyrate formulations that combine immediate release and solid sustained release portions. The claims recite four core inventive features, with further refinements for dissolution thresholds and optional excipients.
Immediate and sustained release gamma-hydroxybutyrate treatment for narcolepsy
Delivering to the patient a formulation comprising immediate release and sustained release portions, each portion comprising at least one pharmaceutically active ingredient selected from gamma-hydroxybutyrate and pharmaceutically acceptable salts of gamma-hydroxybutyrate, for treating cataplexy or excessive daytime sleepiness associated with narcolepsy.
Functional coating deposited over sustained release core with methacrylic acid-methyl methacrylate co-polymers
Sustained release portion comprises a functional coating deposited over a core, wherein the functional coating comprises one or more methacrylic acid-methyl methacrylate co-polymers that are from about 20% to about 50% by weight of the functional coating.
Sustained release dissolution threshold for gamma-hydroxybutyrate
Sustained release portion releases greater than about 40% of its gamma-hydroxybutyrate by about 4 to about 6 hours under defined dissolution apparatus conditions.
Immediate release proportion and gamma-hydroxybutyrate split
Immediate release portion comprises about 75% and about 98% by weight of at least one pharmaceutically active ingredient selected from gamma-hydroxybutyrate and pharmaceutically acceptable salts of gamma-hydroxybutyrate, and the amount of gamma-hydroxybutyrate in the immediate release portion is about 10% to 50% by weight of the total gamma-hydroxybutyrate in the formulation.
Overall early and late dissolution release thresholds
The formulation releases at least about 30% of its gamma-hydroxybutyrate by one hour and releases greater than about 90% of its gamma-hydroxybutyrate by 8 hours under defined dissolution apparatus conditions.
Immediate release excipients selected from copovidone, plasacryl, and cellulose-based excipients
Immediate release portion further comprises one or more pharmaceutically acceptable excipients selected from copovidone, plasacryl, hydroxypropyl cellulose, hydroxypropyl methylcellulose and hydroxymethyl cellulose.
The independent claims collectively cover narcolepsy treatment using gamma-hydroxybutyrate formulations that include immediate release and solid sustained release portions. The sustained release portion is defined by a core with a functional coating comprising methacrylic acid-methyl methacrylate co-polymers and by dissolution release thresholds, while the immediate release portion includes defined gamma-hydroxybutyrate proportions and optional excipients.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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