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-10987310-B2
Publication Date
2021-04-27
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 provides an oral formulation comprising immediate release portions and sustained release portions for gamma-hydroxybutyrate and pharmaceutically acceptable salts of gamma-hydroxybutyrate. The sustained release portion includes a core and a functional coating deposited over the core, wherein the core comprises gamma-hydroxybutyrate or a pharmaceutically acceptable salt and the functional coating comprises one or more methacrylic acid-methyl methacrylate co-polymers in a specified weight proportion.
The formulation is configured to achieve defined dissolution and release behavior under dissolution apparatus conditions in deionized water at 37°C with a paddle speed of 50 rpm. The sustained release portion releases greater than about 40% of its gamma-hydroxybutyrate by about 4 to about 6 hours, while the formulation also releases at least about 30% by one hour and greater than about 90% by 8 hours.
The invention further specifies immediate release excipient selections for the immediate release portion, including pharmaceutically acceptable excipients such as copovidone, plasacryl, hydroxypropyl cellulose, hydroxypropyl methylcellulose and hydroxymethyl cellulose. The formulation includes defined gamma-hydroxybutyrate weight fractions in the immediate release portion and is described in the context of controlled release concepts for highly water-soluble and highly hygroscopic drugs.
Claims Coverage
The partial content contains two independent claims. Both independent claims are directed to formulations combining immediate release and sustained release portions for gamma-hydroxybutyrate and pharmaceutically acceptable salts, with a sustained release portion having a functional coating of methacrylic acid-methyl methacrylate co-polymers and defined dissolution/release thresholds under specified apparatus conditions.
Immediate and sustained release portions for gamma-hydroxybutyrate
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, wherein the sustained release portion comprises a functional coating and a core and the immediate release portion further comprises one or more pharmaceutically acceptable excipients selected from copovidone, plasacryl, hydroxypropyl cellulose, hydroxypropyl methylcellulose and hydroxymethyl cellulose.
Functional coating over core using methacrylic acid-methyl methacrylate co-polymers
The sustained release portion includes a functional coating deposited over the core, wherein the functional coating comprises one or more methacrylic acid-methyl methacrylate co-polymers from about 20% to about 50% by weight of the functional coating.
Defined sustained-release loading and dissolution release thresholds
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, wherein the sustained release portion releases greater than about 40% of its gamma-hydroxybutyrate by about 4 to about 6 hours when tested in a dissolution apparatus in deionized water at a temperature of 37°C and a paddle speed of 50 rpm; the formulation releases at least about 30% of its gamma-hydroxybutyrate by one hour and greater than about 90% of its gamma-hydroxybutyrate by 8 hours under the same dissolution apparatus conditions.
Immediate release portion gamma-hydroxybutyrate fraction range
The immediate release portion comprises an amount of gamma-hydroxybutyrate and pharmaceutically acceptable salts of gamma-hydroxybutyrate of about 10% to 50% by weight of the gamma-hydroxybutyrate and pharmaceutically acceptable salts of gamma-hydroxybutyrate in the formulation.
Solid sustained release portion with specified immediate dose excipient level
A formulation comprising immediate release and a solid sustained release portions, wherein the immediate release portion comprises about 55 mg to 12 g of at least one pharmaceutically active ingredient selected from gamma-hydroxybutyrate and pharmaceutically acceptable salts of gamma-hydroxybutyrate and about 10% by weight of one or more pharmaceutically acceptable excipients selected from the group consisting of copovidone, plasacryl, hydroxypropyl cellulose, hydroxypropyl methylcellulose and hydroxymethyl cellulose.
Across the independent claims, the claim coverage centers on combining immediate release and sustained release portions for gamma-hydroxybutyrate and salts, using a sustained release functional coating deposited over a core with methacrylic acid-methyl methacrylate co-polymers at a specified coating weight fraction, and requiring specific dissolution/release thresholds under deionized water at 37°C with paddle speed 50 rpm.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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