Pharmacokinetics of combined release formulations of gamma-hydroxybutyrate derivatives

Abstract

A pharmaceutical composition comprising an immediate release component comprising 4-((L-valyl)oxy)butanoic acid, and a modified release component comprising 4-((L-valyl)oxy)butanoic acid, and the pharmacokinetics of 4-((L-valyl)oxy)butanoic acid and gamma-hydroxybutyrate following oral administration of the pharmaceutical composition are disclosed.

Claims

1. A pharmaceutical composition, An immediate-release component comprising 2 g to 7 g of 4-((L-valyl)oxy)butanoic acid, A controlled release component comprising 7 g to 15 g of 4-((L-valyl)oxy)butanoic acid, The controlled release component includes controlled release microparticles, The controlled emission microparticles include a core and a controlled emission coating surrounding the core, The core contains more than 90% by weight of 4-((L-valyl)oxy)butanoic acid, and the weight percentage is based on the total weight of the core. The controlled-release microparticles comprise 10% to 35% by weight of the controlled-release coating. The weight % is based on the total weight of the controlled release microparticles. Pharmaceutical composition.

2. The aforementioned immediate-release component contains 10% to 50% by weight of 4-((L-valyl)oxy)butanoic acid, The aforementioned regulated release component contains 50% to 90% by weight of 4-((L-valyl)oxy)butanoic acid, The pharmaceutical composition according to claim 1, wherein the weight percent is based on the total weight of 4-((L-valyl)oxy)butanoic acid in the pharmaceutical composition.

3. The pharmaceutical composition according to claim 1 or 2, wherein the immediate-release component comprises a solution suitable for oral administration.

4. The pharmaceutical composition comprises a solution, The pharmaceutical composition according to claim 1, wherein the controlled release component comprises a suspension of controlled release microparticles suspended in a solution.

5. The pharmaceutical composition according to claim 1, wherein the immediate-release component comprises a plurality of immediate-release microparticles.

6. The pharmaceutical composition according to claim 5, wherein the immediate-release microparticles contain more than 90% by weight of 4-((L-valyl)oxy)butanoic acid, and the weight percentage is based on the total weight of the immediate-release microparticles.

7. The aforementioned immediately released microparticles 95.0% to 99.5% by weight of 4-((L-valyl)oxy)butanoic acid, A flow rate control agent in an amount of 0.1% to 2.0% by weight, and Containing 0.1% to 1.0% by weight of a binder, The pharmaceutical composition according to claim 5, wherein the weight % is based on the total weight of the immediate-release microparticles.

8. The pharmaceutical composition according to claim 5, wherein the immediately released microparticles have a volume average diameter D(4,3) of 200 μm to 500 μm.

9. The aforementioned immediate release component includes immediate release microparticles, The pharmaceutical composition according to claim 1, wherein the regulated release component includes regulated release microparticles.

10. The pharmaceutical composition according to claim 1, wherein the weight ratio of 4-((L-valyl)oxy)butanoic acid in the immediate-release component to 4-((L-valyl)oxy)butanoic acid in the controlled-release component is 1:2 to 1:

3.

11. The aforementioned immediate-release component contains 20% to 40% by weight of 4-((L-valyl)oxy)butanoic acid, The regulated release component comprises 60% to 80% by weight of 4-((L-valyl)oxy)butanoic acid, The pharmaceutical composition according to claim 1, wherein the weight percent is based on the total weight of 4-((L-valyl)oxy)butanoic acid.

12. A pharmaceutical composition according to any one of claims 1 to 11 for the treatment of narcolepsy, excessive daytime sleepiness, cataplexy, excessive daytime sleepiness associated with narcolepsy, excessive daytime sleepiness associated with Parkinson's disease, excessive daytime sleepiness associated with multiple sclerosis, cataplexy associated with narcolepsy, fatigue, fatigue associated with Parkinson's disease, fatigue associated with multiple sclerosis, idiopathic hypersomnia, or fibromyalgia.

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