Solid oral dosage form containing an enhancer
View Patent ↗The invention relates to a pharmaceutical composition and oral dosage forms comprising a bisphosphonate in combination with an enhancer to enhance intestinal delivery of the bisphosphonate to the underlying circulation. Preferably, the enhancer is a medium chain fatty acid or a medium chain fatty acid derivative having a carbon chain length of from 6 to 20 carbon atoms, and the solid oral dosage form is a controlled release dosage form such as a delayed release dosage form.
1. A method for treating or delaying the onset of a medical condition responsive to bisphosphonates comprising the step of administering orally to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition which is effective in delivering a therapeutically effective amount of a bisphosphonate and an enhancer to an intestine, said composition comprising a bisphosphonate and an enhancer wherein the enhancer comprises a salt of a medium chain fatty acid having a carbon chain length of from 8 to 12 carbon atoms and is solid at room temperature.
2. The method of claim 1 , wherein the medical condition is osteoporosis.
3. The method of claim 1 , wherein the medical condition is metastatic bone cancer.
4. The method of claim 1 , wherein the medical condition is rheumatoid arthritis.
5. The method of claim 1 , wherein the medical condition is a bone fracture.
6. The method of claim 1 , wherein the administration step occurs within thirty minutes prior to the patient consuming food, medications, or beverages other than water.
7. The method of claim 1 , wherein the administration step occurs at a time of day other than the morning.
8. The method of claim 1 , wherein the administration step occurs in the evening.
9. The method of claim 1 , wherein the administration occurs within 30 minutes prior to the patient lying down.
10. A method for treating or delaying the onset of a medical condition responsive to bisphosphonates comprising the step of administering orally to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition which is effective in delivering therapeutically effective amounts of a bisphosphonate and an enhancer, wherein the enhancer: (1) comprises a salt of a medium chain fatty acid having a carbon chain length of from 8 to 12 carbon atoms; (2) is the only enhancer present in the composition; and (3) enhances intestinal delivery of the bisphosphonate to the underlying circulation.
11. The method of claim 10 , wherein the administration step occurs within thirty minutes prior to the patient consuming food, medications, or beverages other than water.
12. The method of claim 10 , wherein the administration step occurs at a time of day other than the morning.
13. The method of claim 10 , wherein the administration occurs within 30 minutes prior to the patient lying down.
14. A method for treating or delaying the onset of a medical condition responsive to bisphosphonates comprising the step of administering orally to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a bisphosphonate and an enhancer, wherein the enhancer enhances intestinal delivery of the bisphosphonate to the underlying circulation, wherein the enhancer comprises a salt of a medium chain fatty acid having a carbon chain length of from 8 to 12 carbon atoms and is solid at room temperature, and wherein the composition delivers a therapeutically effective amount of the bisphosphonate when administered to a patient within thirty minutes prior to the patient consuming food, medications, or beverages other than water.
15. A method for treating or delaying the onset of a medical condition responsive to bisphosphonates comprising the step of administering orally to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a bisphosphonate and an enhancer, wherein the enhancer enhances intestinal delivery of the bisphosphonate to the underlying circulation, wherein the enhancer comprises a salt of a medium chain fatty acid having a carbon chain length of from 8 to 12 carbon atoms and is solid at room temperature, and wherein the composition delivers a therapeutically effective amount of the bisphosphonate when administered to a patient at a time of day other than the morning.
16. A method for treating or delaying the onset of a medical condition responsive to bisphosphonates comprising the step of administering orally to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a bisphosphonate and an enhancer, wherein the enhancer enhances intestinal delivery of the bisphosphonate to the underlying circulation, wherein the enhancer comprises a salt of a medium chain fatty acid having a carbon chain length of from 8 to 12 carbon atoms and is solid at room temperature, and wherein the composition delivers a therapeutically effective amount of the bisphosphonate when administered to a patient within 30 minutes prior to the patient lying down.
17. A method for treating or delaying the onset of a medical condition responsive to bisphosphonates comprising the step of administering orally to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a bisphosphonate and an enhancer, wherein the enhancer enhances intestinal delivery of the bisphosphonate to the underlying circulation, wherein the enhancer comprises a salt of a medium chain fatty acid having a carbon chain length of from 8 to 12 carbon atoms and is solid at room temperature, and wherein the composition delivers a therapeutically effective amount of the bisphosphonate when administered to a patient within six hours after consuming food, medications, or beverages other than water.
18. A method for treating or delaying the onset of osteoporosis comprising the step of administering orally to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition which is effective in delivering a therapeutically effective amount of a drug and an enhancer-to an intestine, said composition comprising a bisphosphonate and an enhancer wherein the enhancer comprises a salt of a medium chain fatty acid having a carbon chain length of from 8 to 12 carbon atoms and is solid at room temperature, wherein the administration step occurs weekly.
19. The method of claim 1 , wherein about 1 mg to about 20 mg bisphosphonate is orally administered.
20. The method of claim 1 , wherein about 2 mg to about 7 mg bisphosphonate is orally administered.
21. The method of claim 17 , wherein about 1 mg to about 100 mg bisphosphonate is orally administered.
22. The method of claim 17 , wherein about 1 mg to about 50 mg bisphosphonate is orally administered.
23. The method of claim 1 , wherein the enhancer is a sodium salt of a medium chain fatty acid.
24. The method of claim 23 , wherein the enhancer is selected from the group consisting of sodium caprylate, sodium caprate and sodium laurate.
25. The method of claim 24 , wherein the absorption enhancer is sodium caprate.
26. The method of claim 10 , wherein the enhancer is a sodium salt of a medium chain fatty acid.
27. The method of claim 26 , wherein the enhancer is selected from the group consisting of sodium caprylate, sodium caprate and sodium laurate.
28. The method of claim 27 , wherein the absorption enhancer is sodium caprate.
29. The method of claim 18 , wherein the enhancer is a sodium salt of a medium chain fatty acid.
30. The method of claim 29 , wherein the enhancer is selected from the group consisting of sodium caprylate, sodium caprate and sodium laurate.
31. The method of claim 30 , wherein the absorption enhancer is sodium caprate.