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 a plurality of layered particles having 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, wherein each layered particle comprises (i) a seed core; (ii) a drug layer comprising the sodium phenylbutyrate; (iii) a seal coating; and (iv) a taste-mask coating, wherein the pharmaceutical composition comprises greater than 60% by total weight sodium phenylbutyrate, wherein the taste-mask coating is insoluble at a neutral pH of greater than 5 and soluble at an acidic pH of less than 2, and wherein the pharmaceutical composition comprises about 5% to 25% by total weight taste-mask coating.
2. The pharmaceutical composition of claim 1 , wherein the taste-mask coating is about 5-10% of the total weight.
3. The pharmaceutical composition of claim 1 , wherein the sodium phenylbutyrate comprises about 65% of the total weight.
4. The pharmaceutical composition of claim 1 , wherein the drug layer comprises sodium phenylbutyrate, a binder, and a plasticizer.
5. The pharmaceutical composition of claim 4 , wherein the binder is hydroxypropyl methylcellulose.
6. The pharmaceutical composition of claim 4 , wherein the plasticizer is polyethylene glycol having a molecular weight between 5,000 and 7,000.
7. The pharmaceutical composition of claim 1 , wherein the drug layer comprises about 65% by total weight sodium phenylbutyrate; 5 to 7% by total weight hydroxypropyl methylcellulose; and 0.1 to 1% by total weight polyethylene glycol having a molecular weight between 5,000 and 7,000.
8. The pharmaceutical composition of claim 1 , wherein the taste-mask coating comprises a polymer formed from dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate.
9. The pharmaceutical composition of claim 1 , wherein the taste-mask coating comprises a polymer formed from dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate, a plasticizer, and talc.
10. The pharmaceutical composition of claim 9 , wherein the plasticizer is polyethylene glycol having a molecular weight between 5,000 and 7,000.
11. The pharmaceutical composition of claim 1 , wherein the seed core is about 10 to 20% of the total weight.
12. The pharmaceutical composition of claim 11 , wherein the seed core comprises microcrystalline cellulose.
13. The pharmaceutical composition of claim 1 , further comprising about 8 to 10% by total weight hydroxypropyl methylcellulose.
14. The pharmaceutical composition of claim 1 , further comprising about 0.5 to 3% by total weight polyethylene glycol having a molecular weight between 5,000 and 7,000.
15. The pharmaceutical composition of claim 1 , wherein the taste-mask coating further comprises talc, and wherein the talc is less than about 4% by total weight.
16. The pharmaceutical composition of claim 1 , wherein the seal coating is about 1-5% of the total weight.
17. The pharmaceutical composition of claim 16 , wherein the seal coating comprises a water soluble polymer.
18. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises about 65% by total weight sodium phenylbutyrate, 8 to 10% by total weight hydroxypropyl methylcellulose, 0.5 to 3% by total weight polyethylene glycol having a molecular weight between 5,000 and 7,000, 10 to 20% by total weight microcrystalline cellulose in the seed core, less than 4% talc in the taste-mask coating, and 5 to 10% of a polymer formed from dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate.
19. The pharmaceutical composition of claim 1 , wherein, upon administration to a subject, said composition has equivalent distribution in plasma compared to a sodium phenylbutyrate formulation that does not comprise a taste-mask coating.
20. 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 a modified release formulation of sodium phenylbutyrate.
21. The pharmaceutical composition of claim 1 , said composition scores favorably in a taste test in comparison to a sodium phenylbutyrate formulation that does not comprise a taste-mask coating.
22. The pharmaceutical composition of claim 1 , wherein taste-masking coating is insoluble at pH 6.5-7.5.
23. The pharmaceutical composition or claim 1 , wherein the taste-mask coating is soluble at a pH of less than 2.
24. The pharmaceutical composition of claim 1 , taste-mask coasting is soluble at pH 1-2.