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-11154521-B2
Publication Date
2021-10-26
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 provides a palatable oral sodium phenylbutyrate pharmaceutical composition comprising a plurality of layered particles. The layered particles include 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.
At least 90% of the layered particles are smaller than 500 µm, and the composition includes specified weight percentages of the seed core, sodium phenylbutyrate, and taste-mask coating. The taste-mask coating is pH-sensitive, being insoluble at mouth or neutral pH and soluble in the stomach or at acidic pH.
The layered multiparticulates are described as having functional layer structure such that low dissolution is maintained under neutral-pH conditions while dissolution is achieved under acidic-pH conditions. The document further describes particular layered particle architectures that may include an optional seal coat and excipients in the composition.
Claims Coverage
The independent claim coverage centers on a single independent claim directed to an oral sodium phenylbutyrate composition comprising layered particles with a seed core, a sodium phenylbutyrate drug layer, and a pH-sensitive taste-mask coating made from dimethylaminoethyl methacrylate/butyl methacrylate/methyl methacrylate polymer, together with specific particle size and weight-fraction limitations.
Layered particles with defined size distribution and weight fractions
A pharmaceutical composition for oral administration of sodium phenylbutyrate comprising a plurality of layered particles having a volume-based particle size distribution wherein at least 90% of the layered particles are smaller than 500 µm and wherein the layered particles comprise a seed core, a drug layer comprising sodium phenylbutyrate, and a taste-mask coating; the composition comprises about 10 to 20% by total weight of the seed core, greater than 60% by total weight sodium phenylbutyrate, and about 5% to 25% by total weight taste-mask coating.
Taste-mask coating polymer from dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate
A pharmaceutical composition as defined above wherein the taste-mask coating comprises a polymer formed from dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate.
The independent claim(s) require a specific layered-particle architecture for oral sodium phenylbutyrate with strict particle size and weight-fraction ranges, combined with a taste-mask coating polymer based on dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate.
Stated Advantages
Improved compliance versus unpalatable immediate-release BUPHENYL® due to palatability/taste-masking.
Neutral-pH dissolution is reduced while acidic-pH dissolution is enabled, supporting taste masking in the mouth while allowing dissolution in acidic conditions.
Documented Applications
Therapeutic use for inborn errors of metabolism including Maple Syrup Urine Disease (MSUD) and urea cycle disorders (UCD).
Therapeutic use for neurodegenerative disorders including Parkinson’s disease.
Therapeutic use for additional conditions including spinal muscular atrophy (SMA), dystonia, and inclusion-body myositis.
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