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-10758488-B2
Publication Date
2020-09-01
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 controlled-release dosage forms for gamma-hydroxybutyrate and pharmaceutically acceptable salts of gamma-hydroxybutyrate. A formulation is provided that includes immediate release and sustained release portions, where both portions comprise at least one pharmaceutically active ingredient selected from gamma-hydroxybutyrate and pharmaceutically acceptable salts of gamma-hydroxybutyrate. The sustained release portion is characterized by a functional coating deposited over a core.
The sustained release portion uses a functional coating comprising one or more methacrylic acid-methyl methacrylate co-polymers. The formulation further defines dissolution and release performance, including the amount of gamma-hydroxybutyrate released at defined times under dissolution apparatus 2 conditions in deionized water at 37° C. with a paddle speed of 50 rpm.
The disclosed formulation aims to control early release and maintain sustained release over time by integrating defined immediate and sustained release portions. This design supports unit dosage forms intended to reduce pulsatile plasma levels and improve convenience for high-dose water-soluble and hygroscopic drugs, as described in the document summary.
Claims Coverage
The document provides one independent claim covering a formulation with both immediate release and sustained release portions and multiple inventive features defined by composition and dissolution-release performance.
Immediate and sustained release formulation using gamma-hydroxybutyrate or salts
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.
Functional-coated sustained release portion with methacrylic acid-methyl methacrylate copolymers
The sustained release portion comprises a functional coating and a core, wherein the functional coating is deposited over the core, wherein the core comprises at least one pharmaceutically active ingredient selected from gamma-hydroxybutyrate and pharmaceutically acceptable salts of gamma-hydroxybutyrate, and wherein the functional coating comprises one or more methacrylic acid-methyl methacrylate co-polymers.
Sustained-release core amount and dissolution release profile
The sustained release portion comprises about 500 mg to 12 g of at least one pharmaceutically active ingredient selected from gamma-hydroxybutyrate and pharmaceutically acceptable salts of gamma-hydroxybutyrate, and releases greater than about 40% of its gamma-hydroxybutyrate by about 4 to about 6 hours under the stated dissolution apparatus conditions.
Immediate-release portion defined by gamma-hydroxybutyrate weight fractions
The 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 and pharmaceutically acceptable salts of gamma-hydroxybutyrate in the immediate release portion is about 10% to 50% by weight of the gamma-hydroxybutyrate and pharmaceutically acceptable salts of gamma-hydroxybutyrate in the formulation.
Overall dissolution release constraints for the combined formulation
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 the stated dissolution apparatus conditions.
Overall, the independent claim covers a gamma-hydroxybutyrate or salt formulation that combines defined immediate-release and functional-coated sustained-release portions, with coverage anchored by methacrylic acid-methyl methacrylate copolymer content, a defined sustained-release dose range, and specific dissolution/release performance thresholds.
Stated Advantages
Reduces pulsatile plasma levels and improves convenience.
Documented Applications
Controlled-release dosage forms for high-dose, water-soluble and hygroscopic drugs, especially gamma-hydroxybutyrate (GHB) and sodium oxybate.
Evaluation against sodium oxybate oral solution using plasma pharmacokinetics (Cmax/Cmin and concentration-time profiles).
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