Pharmaceutical composition comprising 3-beta-hydroxy-5-alpha-pregnan-20-one with improved storage and solubility properties
It is provided a pharmaceutical composition comprising 3-beta-hydroxy-5-alpha-pregnan-20-one, at least one sterol or an ester thereof and a mixture of acylglycerols with a solid fat content of less than 25% at 25° C. and 0% at 37° C. In addition it is provided a method for preparing the pharmaceutical composition.
1. A pharmaceutical composition, comprising:
3-beta-hydroxy-5-alpha-pregnan-20-one;
cholesterol; and
a medium-chain triacylglycerol (MCT),
wherein a weight ratio of said cholesterol to said 3-beta-hydroxy-5-alpha-pregnan-20-one is 1:5 to 2:1,
wherein 3-beta-hydroxy-5-alpha-pregnan-20-one is present in an amount of up to 75 mg/g of the composition; and
wherein at room temperature the composition is a liquid oil composition.
2. The pharmaceutical composition according to claim 1 , wherein the MCT comprises a mixture of triacylglycerols which has a total combined percentage of (i) fatty acids with eight carbon atoms and (ii) fatty acids with ten carbon atoms of at least 95%.
3. The pharmaceutical composition according to claim 1 , wherein the 3-beta-hydroxy-5-alpha-pregnan-20-one is suspended in a solution comprising the cholesterol and the MCT.
4. The pharmaceutical composition according to claim 1 , wherein at least some of the 3-beta-hydroxy-5-alpha-pregnan-20-one is dissolved in a solution comprising the cholesterol and the MCT.
5. A pharmaceutical composition according to claim 1 , wherein 3-beta-hydroxy-5-alpha-pregnan-20-one is present in an amount of up to 50 mg/g of the composition.
6. The pharmaceutical composition according to claim 1 , wherein the composition further comprises a vegetable oil, and the vegetable oil is selected from the group consisting of sesame oil, peanut oil, olive oil, and castor oil.
7. The pharmaceutical composition according to claim 1 , wherein said medium-chain triacylglycerol is a mixture of acylglycerols wherein the total combined percentage of fatty acids with 8 carbon atoms and 10 carbon atoms is at least 95%.
8. The pharmaceutical composition according to claim 1 , wherein said medium-chain triacylglycerol comprises at least about 95% triacylglycerols.
9. The pharmaceutical composition according to claim 1 , wherein said medium-chain triacylglycerol is a mixture of acylglycerols wherein the total combined percentage of fatty acids with 8 carbon atoms and 10 carbon atoms is at least 95% and said medium-chain triacylglycerol comprises at least about 95% triacylglycerols.
10. The pharmaceutical composition according to claim 1 , wherein the weight ratio of said cholesterol to said 3-beta-hydroxy-5-alpha-pregnan-20-one is 1:4 to 2:1.
11. The pharmaceutical composition according to claim 1 , wherein the weight ratio of said cholesterol to said 3-beta-hydroxy-5-alpha-prenan-20-one is 1:3 to 2:1.
12. The pharmaceutical composition according to claim 1 , wherein said composition is formulated for parenteral administration.
13. The pharmaceutical composition according to claim 1 , wherein the weight ratio of said cholesterol to said 3-beta-hydroxy-5-alpha-pregnan-20-one is 1:1 to 1:4.
14. The pharmaceutical composition according to claim 1 , wherein the weight ratio of said cholesterol to said 3-beta-hydroxy-5-alpha-pregnan-20-one is 1:2 to 1:4.
15. The pharmaceutical composition according to claim 1 , wherein the weight ratio of said cholesterol to said 3-beta-hydroxy-5-alpha-pregnan-20-one is 1:2.5 to 1.2:1.
16. The pharmaceutical composition according to claim 1 , wherein the concentration of said cholesterol is no more than about 30 mg/ml.
17. The pharmaceutical composition according to claim 1 , wherein 3-beta-hydroxy-5-alpha-pregnan-20-one is present in an amount of up to 40 mg/g of the composition.
18. The pharmaceutical composition according to claim 1 , wherein 3-beta-hydroxy-5-alpha-pregnan-20-one is present in an amount of 25-40 mg/g of the composition.
19. A method of terminating steroid induced anesthesia, comprising: administering the pharmaceutical composition according to claim 1 to a subject in need thereof.