Compositions for delivery of insoluble agents
View Patent ↗Compositions and methods of making the same for in vivo delivery of lixivaptan to a subject in need thereof are described. The composition includes a substantially water-insoluble pharmacologically active agent (e.g., lixivaptan) and a substantially water-insoluble matrix forming material (e.g., a Vitamin E semi-ester), wherein the pharmacologically active agent is dispersed in said matrix forming material, and wherein the composition delivers said substantially water-insoluble pharmacologically active agent upon exposure to physiological medium.
1. A pharmaceutical composition comprising a single oral dosage form including an oil-free and substantially water-free solid dispersion, the dispersion including a therapeutically effective amount of lixivaptan and 50% or more by weight of a vitamin E semi-ester.
2. The composition of claim 1 , wherein the dispersion further includes a surfactant.
3. The composition of claim 2 , wherein the surfactant is an alkyl sulfate salt.
4. The composition of claim 3 , wherein the alkyl sulfate salt is sodium lauryl sulfate.
5. The composition of claim 1 , wherein the dispersion is substantially free of crystalline lixivaptan.
6. The composition of claim 1 , wherein the dispersion includes 60% or more by weight of vitamin E semi-ester.
7. The composition of claim 1 further including a disintegrant.
8. The composition of claim 7 , wherein the disintegrant is a crosslinked poly(vinylpyrrolidone).
9. The composition of claim 1 , wherein the dispersion further includes a water soluble polymer.
10. The composition of claim 1 , the dispersion further includes a plant protein.
11. The composition of claim 10 , wherein the plant protein is zein.
12. The composition of claim 1 further including a surfactant.
13. The composition of claim 12 , wherein the surfactant is an alkyl sulfate salt.
14. The composition of claim 13 , wherein the alkyl sulfate salt is sodium lauryl sulfate.
15. The composition of claim 1 , wherein the vitamin E semi-ester is alpha-tocopheryl succinate.
16. A method of making a pharmaceutical composition comprising:
dissolving an amount of lixivaptan in a non-aqueous solvent;
dissolving an amount of a vitamin E semi-ester derivative in the non-aqueous solvent; and
removing the solvent, thereby forming a solid dispersion including lixivaptan and the vitamin E semi-ester derivative.
17. The method of claim 16 , wherein the vitamin E semi-ester derivative is alphatocopheryl succinate.
18. The method of claim 16 , further comprising mixing the solid dispersion with a disintegrant.
19. The method of claim 18 , further comprising mixing the solid dispersion with a surfactant.
20. The method of claim 16 , further comprising dissolving an amount of a water-soluble protein in the non-aqueous solvent.
21. The method of claim 20 , wherein removing the solvent includes spray drying.
22. The method of claim 16 , wherein the dispersion is substantially free of crystalline lixivaptan.