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 - 30 . (canceled)
31 . A pharmaceutical composition for oral administration of sodium phenylbutyrate comprising a plurality of layered particles, wherein each layered particle comprises (i) a substrate; (ii) a drug layer comprising the sodium phenylbutyrate; and (iii) a taste-mask coating insoluble at a pH of greater than 5, wherein the pharmaceutical composition comprises greater than 60% by total weight sodium phenylbutyrate.
32 . The pharmaceutical composition of claim 31 , wherein each of the plurality of layered particles has a size from about 100 μm to 1,500 μm.
33 . The pharmaceutical composition of claim 31 , wherein the plurality of layered particles comprises a volume-based particle size distribution in which at least 90% of the layered particles in the plurality of layered particles are smaller than 500 μm.
34 . The pharmaceutical composition of claim 31 , wherein the substrate is a seed core.
35 . The pharmaceutical composition of claim 31 , further comprising a seal coating.
36 . The pharmaceutical composition of claim 31 , wherein the drug layer comprises the sodium phenylbutyrate, a binder, and a plasticizer.
37 . The pharmaceutical composition of claim 31 , wherein the taste-mask coating is insoluble at a pH of 6.5-7.5.
38 . The pharmaceutical composition of claim 31 , wherein the taste-mask coating is soluble at an acidic pH of less than 2.
39 . The pharmaceutical composition of claim 31 , wherein the pharmaceutical composition comprises at least 5% by total weight taste-mask coating.
40 . The pharmaceutical composition of claim 31 , wherein the taste-mask coating comprises a polymer.
41 . The pharmaceutical composition of claim 31 , wherein the taste-mask coating comprises a polymer formed from dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate.
42 . The pharmaceutical composition of claim 31 , wherein the taste-mask coating further comprises a hydrated magnesium silicate and/or a plasticizer.
43 . The pharmaceutical composition of claim 31 , further comprising a glidant.
44 . The pharmaceutical composition of claim 31 , wherein the composition is a powder, granules, or a tablet.
45 . The pharmaceutical composition of claim 31 , wherein upon administration to a subject, said composition has an equivalent distribution in plasma compared to a sodium phenylbutyrate formulation that does not comprise a taste-mask coating.
46 . The pharmaceutical composition of claim 31 , wherein upon administration to a subject, said composition has greater sodium phenylbutyrate levels in the plasma at 30 minutes compared to a modified release formulation of sodium phenylbutyrate.
47 . A method of treating an inborn error of metabolism in a subject, the method comprising orally administering the pharmaceutical composition of claim 31 .
48 . The method of claim 47 , wherein the subject is human.
49 . The method of claim 47 , wherein (i) subjects under 20 kg are administered 450-600 mg/kg/day of sodium phenylbutyrate; and (ii) subjects over 20 kg are administered 9.9-13.0 g/m2/day of sodium phenylbutyrate.
50 . The method of claim 47 , wherein the inborn error of metabolism is a urea cycle disorder or maple syrup disease.