Modified release compositions of a gamma-hydroxybutyric acid derivative
Pharmaceutical granulations having a functional coating surrounding a core containing 4-((L-valyl)oxy)butanoic acid are disclosed. The functional coatings provide for immediate release or modified release of 4-((L-valyl)oxy)butanoic acid. The pharmaceutical granulations can be used in oral pharmaceutical compositions.
1. A pharmaceutical composition comprising:
(a) an immediate release component, wherein the immediate release component comprises:
from 2 g to 8 g of 4-((L-valyl)oxy)butanoic acid; and
a plurality of granules, wherein,
the granules comprise greater than 80 wt % of 4-((L-valyl)oxy)butanoic acid, wherein wt % is based on the total weight of the granules; and
the granules have an average particle diameter (D50) from 75 μm to 450 μm as determined by sieve analysis or by laser diffraction; and
(b) a modified release component, wherein the modified release component comprises:
from 8 g to 16 g of 4-((L-valyl)oxy)butanoic acid; and
a plurality of coated granules, wherein,
the coated granules have an average particle diameter (D50) from 150 μm to 400 μm as determined by sieve analysis or by laser diffraction;
the coated granules comprise a core and a modified release coating surrounding the core;
the core comprises greater than 85 wt % of 4-((L-valyl)oxy)butanoic acid, wherein wt % is based on the total weight of the core; and
the modified release coating comprises:
from 70 wt % to 95 wt % of a matrix polymer; and
from 5 wt % to 30 wt % of a first antistatic agent;
wherein wt % is based on the total weight of the modified release coating.
2. The pharmaceutical composition of claim 1 , wherein the core comprises greater than 90 wt % of γ-((L-valyl)oxy)butanoic acid, wherein wt % is based on the total weight of the core.
3. The pharmaceutical composition of claim 1 , wherein the core comprises:
greater than 85 wt % of γ-((L-valyl)oxy)butanoic acid;
from 1 wt % to 10 wt % of a second antistatic agent; and
from 1 wt % to 10 wt % of a water-soluble polymer,
wherein wt % is based on the total weight of the core.
4. The pharmaceutical composition of claim 3 , wherein,
the second antistatic agent comprises talc; and
the water-soluble polymer comprises hydroxypropylmethyl cellulose.
5. The pharmaceutical composition of claim 1 , wherein the matrix polymer comprises a water-soluble polymer and a water insoluble polymer.
6. The pharmaceutical composition of claim 5 , wherein the modified release coating comprises:
from 72 wt % to 92 wt % of the water-insoluble polymer; and
from 0.1 wt % to 10 wt % of the water-soluble polymer,
wherein wt % is based on the total weight of the modified release coating.
7. The pharmaceutical composition of claim 5 , wherein,
the water-insoluble polymer comprises ethylcellulose; and
the water-soluble polymer comprises hydroxypropyl cellulose.
8. The pharmaceutical composition of claim 1 , wherein the first antistatic agent is selected from the group consisting of talc, magnesium stearate, and a combination thereof.
9. The pharmaceutical composition of claim 1 , wherein the coated granules comprise:
from 65 wt % to 85 wt % of the core; and
from 15 wt % to 40 wt % of the modified release coating;
wherein wt % is based on the total weight of the coated granules.
10. The pharmaceutical composition of claim 1 , wherein the modified release coating does not comprise a plasticizer.
11. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises from 10 g to 20 g of 4-((L-valyl)oxy)butanoic acid.
12. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises the modified release component suspended in a solution of the immediate release component.
13. The pharmaceutical composition of claim 1 , wherein the coated granules comprise from 10 wt % to 50 wt % of the modified release coating, wherein wt % is based on the total weight of the coated granules.
14. The pharmaceutical composition of claim 1 , wherein the matrix polymer comprises:
from 92 wt % to 98 wt % of a water-insoluble polymer; and
from 2 wt % to 8 wt % of a water-soluble polymer.
15. The pharmaceutical composition of claim 1 , wherein the first antistatic agent is talc.
16. The pharmaceutical composition of claim 1 , wherein the first antistatic agent is magnesium stearate.
17. The pharmaceutical composition of claim 1 , wherein the modified release coating comprises a plasticizing agent.
18. The pharmaceutical composition of claim 17 , wherein the plasticizing agent is dibutyl sebacate.