Pharmaceutical compositions and related methods of delivery
The pharmaceutical compositions described herein include a suspension which comprises an admixture in solid form of a therapeutically effective amount of a therapeutic agent and at least one salt of a medium chain fatty acid and a hydrophobic medium, e.g. castor oil or glyceryl tricaprylate or a mixture thereof. The pharmaceutical compositions described herein contain medium chain fatty acid salts and are substantially free of alcohols. The pharmaceutical compositions may be encapsulated in a capsule. Methods of treating or preventing diseases by administering such compositions to affected subjects are also disclosed.
1. An enteric-coated oral dosage form comprising a composition comprising a suspension which comprises an admixture of a hydrophobic medium and a solid form wherein the solid form comprises a therapeutically effective amount of octreotide, at least one salt of a medium chain fatty acid and polyvinylpyrrolidone (PVP), wherein the polyvinylpyrrolidone is present in the composition at an amount of 3% or more by weight, and wherein the at least one salt of a medium chain fatty acid salt is present in the composition at an amount of at least 12% or more by weight.
2. The enteric-coated oral dosage form of claim 1 , wherein the medium chain fatty acid salt is present in the composition at an amount of 12% to 40% by weight.
3. The enteric-coated oral dosage form of claim 2 wherein the medium chain fatty acid salt is present in the composition at an amount of 12% to 18% by weight.
4. The enteric-coated oral dosage form of claim 1 where the polyvinylpyrrolidone is present in the composition at an amount of about 3% to about 20% by weight.
5. The enteric-coated oral dosage form of claim 4 where the polyvinylpyrrolidone is present in the composition at an amount of about 5% to about 15% by weight.
6. The enteric-coated oral dosage form of claim 1 , wherein the hydrophobic medium comprises glyceryl tricaprylate and the solid form consists of polyvinylpyrrolidone with a molecular weight of about 3000, and sodium octanoate.
7. The enteric-coated oral dosage form of claim 1 wherein the hydrophobic medium additionally comprises castor oil or glyceryl monocaprylate or a combination thereof and a surfactant.
8. The enteric-coated oral dosage form of claim 1 wherein the hydrophobic medium consists of glyceryl tricaprylate, glyceryl monocaprylate, and polyoxyethylene sorbitan monooleate.
9. The enteric-coated oral dosage form of claim 1 wherein the solid form consists essentially of octreotide, polyvinylpyrrolidone with a molecular weight of about 3000, and sodium octanoate.
10. The enteric-coated oral dosage form of claim 1 wherein the composition comprises about 41% of glyceryl tricaprylate, about 27% castor oil, about 4% glyceryl monocaprylate, about 2% polyoxyethylene sorbitan monooleate, about 15% sodium octanoate, about 10% polyvinylpyrrolidone with a molecular weight of about 3000, about 1% water and about 0.058% by weight octreotide.
11. The enteric-coated oral dosage form of claim 1 wherein the composition comprises about 68% glyceryl tricaprylate, about 4% glyceryl monocaprylate, about 2% polyoxyethylene sorbitan monooleate, about 15% sodium octanoate, about 10% polyvinylpyrrolidone with a molecular weight of about 3000, about 1% water and about 0.058% by weight octreotide.
12. The enteric-coated oral dosage form of claim 1 , wherein the composition comprises a therapeutically effective amount of octreotide, about 12-21% of sodium octanoate, about 5-10% of polyvinylpyrrolidone with a molecular weight of about 3000, about 20-80% of glyceryl tricaprylate, about 0-50% castor oil, about 3-10% surfactant and about 1% by weight water.
13. The enteric-coated oral dosage form of claim 1 , wherein the composition comprises a therapeutically effective amount of octreotide, about 12-21% of sodium octanoate, about 5-10% of polyvinylpyrrolidone with a molecular weight of about 3000, about 20-80% of glyceryl tricaprylate, about 3-10% surfactant and about 1% by weight water.
14. The enteric-coated oral dosage form of claim 13 , wherein the octreotide is present at an amount of less than 33%.
15. The enteric-coated oral dosage form of claim 14 , wherein the composition comprises about 15% of sodium octanoate, about 10% of polyvinylpyrrolidone with a molecular weight of about 3000, about 30-70% glyceryl tricaprylate and about 6% of surfactant.
16. The enteric-coated oral dosage form of claim 15 , wherein the surfactant is glyceryl monocaprylate or polyoxyethylene sorbitan monooleate.
17. The enteric-coated oral dosage form of claim 1 , wherein the solid form comprises a particle or a plurality of particles.
18. The enteric-coated oral dosage form of claim 16 , wherein the solid form further comprises a stabilizer.
19. The enteric-coated oral dosage form of claim 1 , wherein the solid form further comprises a stabilizer.
20. The enteric-coated oral dosage form of claim 1 , wherein the fatty acid is octanoic acid.
21. The enteric-coated oral dosage form of claim 13 , wherein the octreotide is present at an amount of less than 25%.
22. The enteric-coated oral dosage form of claim 13 , wherein the octreotide is present at an amount of less than 10%.
23. The enteric-coated oral dosage form of claim 13 , wherein the octreotide is present at an amount of less than 1%.
24. The enteric-coated oral dosage form of claim 13 , wherein the octreotide is present at an amount of less than 0.1%.
25. The enteric-coated oral dosage form of claim 1 , wherein the polyvinylpyrrolidone has a molecular weight of about 3000.
26. The enteric-coated oral dosage form of claim 1 , wherein the medium chain fatty acid salt has a chain length from about 6 to about 14 carbon atoms.
27. The enteric-coated oral dosage form of claim 26 , wherein the medium chain fatty acid salt is sodium hexanoate, sodium heptanoate, sodium octanoate, sodium nonanoate, sodium decanoate, sodium undecanoate, sodium dodecanoate, sodium tridecanoate or sodium tetradecanoate, or a corresponding potassium or lithium or ammonium salt or a combination thereof.
28. The enteric-coated oral dosage form of claim 27 , wherein the medium chain fatty acid salt is sodium octanoate.
29. The enteric-coated oral dosage form of claim 1 , wherein the hydrophobic oily medium comprises a mineral oil, a paraffin, a fatty acid a monoglyceride, a diglyceride, a triglyceride, an ether or an ester, or a combination thereof.
30. The enteric-coated oral dosage form of claim 1 , wherein the medium chain fatty acid salt is a lithium, potassium or ammonium salt.
31. The enteric-coated oral dosage form of claim 1 , wherein the hydrophobic oily medium comprises glyceryl tricaprylate.
32. The enteric-coated oral dosage form of claim 1 , wherein the composition further comprises a surfactant.