Palatable compositions including sodium phenylbutyrate and uses thereof
Inventors
Appel, Leah E. • Shockey, Joshua R. • SCHELLING, D. Christopher
Assignees
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Publication Number
US-11433041-B2
Publication Date
2022-09-06
Expiration Date
Abstract
The present invention features palatable pharmaceutical compositions including sodium phenylbutyrate and methods for the treatment of inborn errors of metabolism (e.g., Maple Syrup Urine Disease or Urea Cycle Disorders), neurodegenerative disorders such as Parkinson's disease, spinal muscular atrophy, dystonia, or inclusion-body myositis with such compositions.
Core Innovation
The invention relates to palatable oral sodium phenylbutyrate pharmaceutical compositions that include layered particles and taste-mask coatings. The layered particles include a seed core, a drug layer comprising sodium phenylbutyrate, a seal coating, and a taste-mask coating. The compositions are formulated such that the taste-mask coating is insoluble at a neutral pH greater than 5 and soluble at an acidic pH less than 2.
The invention addresses oral administration of sodium phenylbutyrate by providing taste-masked compositions with high drug-loading. The compositions comprise greater than 60% by total weight sodium phenylbutyrate and further comprise about 5% to 25% by total weight taste-mask coating. The layered particles have a volume-based particle size distribution in which at least 90% of the layered particles are smaller than 500 μm.
The disclosed formulations are evaluated using dissolution transfer test criteria, including low release at neutral pH and high dissolution at acidic pH. The document also discusses improved compliance, including comparative taste test performance and bioequivalence/comparable plasma distribution versus marketed references such as BUPHENYL® and RAVICTI®.
Claims Coverage
The partial content provides one independent claim covering a layered, taste-masked, pH-responsive oral sodium phenylbutyrate composition with defined particle size distribution and defined solubility behavior of the taste-mask coating. The independent claim contains multiple main inventive features.
Layered particles with seed core, drug layer, seal coating, and taste-mask coating
Each layered particle comprises a seed core, a drug layer comprising sodium phenylbutyrate, a seal coating, and a taste-mask coating.
Defined volume-based particle size distribution for layered particles
The plurality of layered particles has a volume-based particle size distribution in which at least 90% of the layered particles are smaller than 500 μm.
High drug loading of sodium phenylbutyrate
The pharmaceutical composition comprises greater than 60% by total weight sodium phenylbutyrate.
pH-responsive taste-mask coating insoluble at neutral pH and soluble at acidic pH
The taste-mask coating is insoluble at a neutral pH of greater than 5 and soluble at an acidic pH of less than 2.
Taste-mask coating content range
The pharmaceutical composition comprises about 5% to 25% by total weight taste-mask coating.
Overall, the independent claim defines an oral sodium phenylbutyrate composition built from layered particles with a specified size distribution, high sodium phenylbutyrate loading, and a taste-mask coating designed to be insoluble at neutral pH and soluble at acidic pH.
Stated Advantages
Improved compliance.
Taste-masked performance in taste testing versus a reference composition such as BUPHENYL®.
Comparable or improved bioequivalence/comparable plasma distribution versus reference products such as RAVICTI® and BUPHENYL®.
Documented Applications
Therapeutic use in inborn errors of metabolism including MSUD and UCD.
Therapeutic use in neurodegenerative/muscle disorders including Parkinson’s disease, spinal muscular atrophy (SMA), dystonia, and inclusion-body myositis.
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