Methods of treating urea cycle disorders and maple syrup urine disease
Inventors
Appel, Leah E. • Shockey, Joshua R. • SCHELLING, D. Christopher
Assignees
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Publication Number
US-11202767-B2
Publication Date
2021-12-21
Expiration Date
Abstract
The present invention provides methods for the treatment of urea cycle disorders and Maple Syrup Urine Disease.
Core Innovation
The invention provides orally administered pharmaceutical compositions of taste-masked, layered particles containing sodium phenylbutyrate. The particles comprise a seed core, a drug layer comprising sodium phenylbutyrate, and a taste-mask coating formed from dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate. The layered particles are characterized by a volume-based particle size distribution in which at least 90% of the layered particles are smaller than 500 μm.
The formulation further specifies component weight proportions, including about 10 to 20% by total weight of the seed core, about 5% to 25% by total weight of the taste-mask coating, and greater than 60% by total weight of the sodium phenylbutyrate. The taste-masked layered particle approach is described in a context of pH-sensitive behavior and transfer dissolution concepts, including transfer dissolution criteria at neutral pH and acidic pH and related performance considerations.
The invention applies these taste-masked, layered particle compositions to treating urea cycle disorders and maple syrup urine disease by administering a therapeutically effective amount of sodium phenylbutyrate to a subject in need thereof. The document describes the treatment context in terms of ammonia removal for urea cycle disorders and provides related pharmacokinetics/bioequivalence and taste-evaluation comparisons to bovine phenylbutyrate formulations, including BUPHENYL® and RAVICTI®.
Claims Coverage
The partial content includes two independent claims covering oral treatment using therapeutically effective sodium phenylbutyrate administered as taste-masked, layered particles with specified particle size distribution and specific formulation component proportions and coating polymer composition.
Taste-masked layered particles for urea cycle disorder treatment
Orally administering a therapeutically effective amount of sodium phenylbutyrate in a pharmaceutical composition comprising a plurality of taste-masked, layered particles with a volume-based particle size distribution in which at least 90% of the layered particles are smaller than 500 μm, wherein the layered particles comprise a seed core, a drug layer comprising sodium phenylbutyrate, and a taste-mask coating comprising a polymer formed from dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate, and wherein the pharmaceutical composition comprises about 10 to 20% by total weight of the seed core, about 5% to 25% by total weight of the taste-mask coating, and greater than 60% by total weight of the sodium phenylbutyrate.
Taste-masked layered particles for maple syrup urine disease treatment
Orally administering a therapeutically effective amount of sodium phenylbutyrate in a pharmaceutical composition comprising a plurality of taste-masked, layered particles with a volume-based particle size distribution in which at least 90% of the layered particles are smaller than 500 μm, wherein the layered particles comprise a seed core, a drug layer comprising sodium phenylbutyrate, and a taste-mask coating comprising a polymer formed from dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate, and wherein the pharmaceutical composition comprises about 10 to 20% by total weight of the seed core, about 5% to 25% by total weight of the taste-mask coating, and greater than 60% by total weight of the sodium phenylbutyrate.
Both independent claims broadly cover oral sodium phenylbutyrate treatment in subjects with urea cycle disorders or maple syrup urine disease using taste-masked, layered seed-core particles with a defined volume-based particle size distribution threshold, defined component weight proportions, and a taste-mask coating polymer formed from dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate.
Stated Advantages
Improved taste via taste-masked pharmaceutical compositions.
Formulation performance considerations including bioequivalence are addressed through related comparisons.
Documented Applications
Treating urea cycle disorders by orally administering a therapeutically effective amount of sodium phenylbutyrate using the specified taste-masked, layered particles.
Treating maple syrup urine disease by orally administering a therapeutically effective amount of sodium phenylbutyrate using the specified taste-masked, layered particles.
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