Controlled release dosage forms for high dose, water soluble and hygroscopic drug substances

Inventors

Allphin, Clark • Pfeiffer, James

Assignees

Jazz Pharmaceuticals Inc

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 treating cataplexy or excessive daytime sleepiness associated with narcolepsy by delivering a formulation that includes a sustained release portion. The sustained release portion comprises a functional coating and a core, where the functional coating is deposited over the core, and the core comprises gamma-hydroxybutyrate (GHB) or pharmaceutically acceptable salts of GHB as the pharmaceutically active ingredient.

A key aspect of the sustained release portion is the use of a functional coating comprising one or more methacrylic acid-methyl methacrylate co-polymers. The functional coating is defined such that the methacrylic acid-methyl methacrylate co-polymers are from about 20% to about 50% by weight of the functional coating.

The sustained release performance is defined by dissolution behavior in deionized water at 37° C in a dissolution apparatus 2 with a paddle speed of 50 rpm, including releasing greater than about 40% of gamma-hydroxybutyrate by about 4 to about 6 hours. The disclosed dosage form concept supports time-dependent delivery intended to provide consistent sustained release of GHB over the stated period under the specified dissolution conditions.

Claims Coverage

The patent family includes at least one independent method claim and multiple dependent claims refining the formulation and dissolution performance. Across the disclosed set, the core coverage centers on a sustained-release GHB formulation with a coated core using methacrylic acid-methyl methacrylate co-polymers, together with dissolution release criteria under specified apparatus conditions.

Overall, the claim coverage is directed to a method of treating narcolepsy-associated cataplexy or excessive daytime sleepiness using a sustained-release GHB formulation built from a coated core. The functional coating uses methacrylic acid-methyl methacrylate co-polymers at defined weight percentages, and the sustained release portion is constrained by a dissolution release criterion in deionized water at 37° C in dissolution apparatus 2 at a paddle speed of 50 rpm, with dependent claims further refining inclusion of an immediate-release portion, excipients, and GHB salt forms.

Stated Advantages

Documented Applications