PALATABLE COMPOSITIONS INCLUDING SODIUM PHENYLBUTYRATE AND USES THEREOF
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.
1 . A pharmaceutical composition for oral administration of sodium phenylbutyrate comprising 15-65% by total weight of said sodium phenylbutyrate and 5-50% by total weight of a taste-mask coating comprising a polymer formed from dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate.
2 . The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated as a plurality of spray-layered beads comprising a seed core, a drug layer comprising said sodium phenylbutyrate, and said taste-mask coating.
3 . The pharmaceutical composition of claim 1 , wherein said taste-mask coating comprises 5-30% by total weight of a polymer formed from dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate.
4 . The pharmaceutical composition of claim 1 , wherein said composition comprises 15-65% by total weight of said taste-mask coating.
5 . The pharmaceutical composition of claim 1 , wherein said composition comprises 15-35% by total weight of sodium phenylbutyrate.
6 . The pharmaceutical composition of claim 2 , wherein said composition has a volume-based particle size distribution in which 90% of the sample is smaller than 500 μm.
7 . The pharmaceutical composition of claim 1 , wherein less than 15% of said sodium phenylbutyrate in the composition is dissolved in a transfer dissolution test at neutral pH over a period of 10 minutes.
8 . The pharmaceutical composition of claim 1 , wherein at least 95% of sodium phenylbutyrate in the composition is dissolved in a transfer dissolution test at an acidic pH over a period of 60 minutes.
9 . The pharmaceutical composition of claim 1 , wherein, upon administration to a subject, said composition has equivalent distribution in plasma compared to BUPHENYL®.
10 . The pharmaceutical composition of claim 1 , wherein, upon administration to a subject, said composition has greater sodium phenylbutyrate levels in the plasma at 30 minutes compared to an modified release formulation of sodium phenylbutyrate.
11 . The pharmaceutical composition of claim 1 , wherein said composition scores favorably in a taste test in comparison to BUPHENYL®.
12 . A taste-masked pharmaceutical composition comprising sodium phenylbutyrate and a pharmaceutically acceptable carrier, wherein (i) less than 15% of the sodium phenylbutyrate in the composition dissolves in a transfer dissolution test at neutral pH over a period of 10 minutes; and (ii) at least 95% of the sodium phenylbutyrate in the composition dissolves in a transfer dissolution test at an acidic pH over a period of 60 minutes.
13 . The pharmaceutical composition of claim 12 , wherein the composition comprises a taste-mask coating comprising a polymer formed from dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate.
14 . The pharmaceutical composition of claim 12 , wherein the composition comprises 5-50% by total weight of the taste-mask coating.
15 . The pharmaceutical composition of claim 12 , wherein the composition comprises 15-60% by total weight of sodium phenylbutyrate.
16 . The pharmaceutical composition of claim 12 , wherein said composition is formulated as a plurality of spray-layered beads.
17 . The pharmaceutical composition of claim 16 , wherein said composition has a volume-based particle size distribution in which 90% of the sample is smaller than approximately 500 μm
18 . The pharmaceutical composition of claim 12 , wherein less than 15% of said sodium phenylbutyrate in the composition is dissolved in a transfer dissolution test at neutral pH over a period of 10 minutes.
19 . The pharmaceutical composition of claim 12 , wherein at least 95% of sodium phenylbutyrate in the composition is dissolved in a transfer dissolution test at an acidic pH over a period of 60 minutes.
20 . The pharmaceutical composition of claim 12 , wherein, upon administration to a subject, said composition has equivalent distribution in plasma compared to BUPHENYL®.
21 . The pharmaceutical composition of claim 12 , wherein, upon administration to a subject, said composition has greater sodium phenylbutyrate levels in the plasma at 30 minutes compared to an modified release formulation of sodium phenylbutyrate.
22 . The pharmaceutical composition of claim 12 , wherein said composition scores favorably in a taste test in comparison to BUPHENYL®.
23 . A method of producing a pharmaceutical composition comprising sodium phenyl butyrate, the method comprising:
a. providing a core comprising cellulose pellets;
b. applying a first layer comprising sodium phenylbutyrate, hydroxypropyl methylcellulose, and a polyethylene glycol;
c. applying a second layer comprising a polyvinyl alcohol; and
d. applying a third layer comprising a polymer formed from dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate, a polyethylene glycol, and hydrated magnesium silicate,
thereby producing a pharmaceutical composition comprising sodium phenyl butyrate.
24 . The method of claim 23 , wherein said composition comprises a first layer including 20-60% by total weight of sodium phenylbutyrate, 3-10% by total weight of hydroxypropyl methylcellulose, and less than 1% by total weight of polyethylene glycol.
25 . The method of claim 23 , wherein said composition comprises a third layer including 10-15% by total weight of a polymer formed from dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate, 3-10% by total weight of polyethylene glycol, and 4-15% by total weight of hydrated magnesium silicate.
26 . A method of treating an inborn error of metabolism in a subject comprising administering an effective amount of a pharmaceutical composition of claim 1 .
27 . The method of claim 26 , wherein the in born error of metabolism is maple syrup urine disease
28 . The method of claim 26 wherein the in born error of metabolism is a urea cycle disorder
29 . The method of claim 26 , wherein the subject is a human.
30 . The method of claim 26 , wherein said composition is administered in combination with a dosing vehicle and a liquid such that the final viscosity is in the range of approximately 50-1750 cP.