Crystallization method and bioavailability
Preparation, in-vitro and in vivo characterization of novel forms of (1-hydroxy-2-imidazol-1-yl-1-phosphono-ethyl)phosphonic acid, suitable for pharmaceutical compositions in drug delivery systems for humans.
1. A molecular complex comprising zoledronic acid and lysine, wherein the molecular complex is a solid.
2. A pharmaceutical composition comprising a molecular complex of claim 1 and a pharmaceutically acceptable excipient.
3. A pharmaceutical composition according to claim 2 , wherein the composition is an oral solid dosage form.
4. The pharmaceutical composition according to claim 3 , wherein the composition is an oral dosage form selected from a tablet and a capsule.
5. A composition comprising a molecular complex of claim 2 and an excess amount of lysine.
6. A molecular complex of claim 1 , wherein the molecular complex is crystalline.
7. A pharmaceutical composition comprising a molecular complex of claim 6 and a pharmaceutically acceptable excipient.
8. A pharmaceutical composition according to claim 7 , wherein the composition is an oral solid dosage form.
9. The pharmaceutical composition according to claim 8 , wherein the composition is an oral dosage form selected from a tablet and a capsule.
10. A composition comprising a molecular complex of claim 6 and an excess amount of lysine.
11. A molecular complex comprising zoledronic acid or a salt thereof and lysine, wherein the molecular complex is a solid and the bioavailability of the zoledronic acid or salt thereof from the molecular complex is greater than the bioavailability of the zoledronic acid or salt thereof without lysine.
12. A pharmaceutical composition comprising a molecular complex of claim 11 and a pharmaceutically acceptable excipient.
13. A pharmaceutical composition according to claim 12 , wherein the composition is an oral solid dosage form.
14. The pharmaceutical composition according to claim 13 , wherein the composition is an oral dosage form selected from a tablet and a capsule.
15. A composition comprising a molecular complex of claim 11 and an excess amount of lysine.
16. A molecular complex of claim 11 , wherein the molecular complex is crystalline.
17. A pharmaceutical composition comprising a molecular complex of claim 16 and a pharmaceutically acceptable excipient.
18. A pharmaceutical composition according to claim 17 , wherein the composition is an oral solid dosage form.
19. The pharmaceutical composition according to claim 18 , wherein the composition is an oral dosage form selected from a tablet and a capsule.
20. A composition comprising a molecular complex of claim 16 and an excess amount of lysine.
21. A method for the treatment of disease states associated with osteoporosis, hypercalcemia, cancer induced bone metastasis, Paget's disease or adjuvant or neoadjuvant cancer therapies comprising the step of administering to a patient in need thereof a therapeutically effective amount of the molecular complex according to claim 1 .
22. A method for the treatment of disease states associated with osteoporosis, hypercalcemia, cancer induced bone metastasis, Paget's disease or adjuvant or neoadjuvant cancer therapies comprising the step of administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical composition according to claim 2 .
23. A method for the treatment of disease states associated with osteoporosis, hypercalcemia, cancer induced bone metastasis, Paget's disease or adjuvant or neoadjuvant cancer therapies comprising the step of administering to a patient in need thereof a therapeutically effective amount of the molecular complex according to claim 6 .
24. A method for the treatment of disease states associated with osteoporosis, hypercalcemia, cancer induced bone metastasis, Paget's disease or adjuvant or neoadjuvant cancer therapies comprising the step of administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical composition according to claim 7 .
25. A method for the treatment of disease states associated with osteoporosis, hypercalcemia, cancer induced bone metastasis, Paget's disease or adjuvant or neoadjuvant cancer therapies comprising the step of administering to a patient in need thereof a therapeutically effective amount of the molecular complex according to claim 11 .
26. A method for the treatment of disease states associated with osteoporosis, hypercalcemia, cancer induced bone metastasis, Paget's disease or adjuvant or neoadjuvant cancer therapies comprising the step of administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical composition according to claim 12 .
27. A method for the treatment of disease states associated with osteoporosis, hypercalcemia, cancer induced bone metastasis, Paget's disease or adjuvant or neoadjuvant cancer therapies comprising the step of administering to a patient in need thereof a therapeutically effective amount of the molecular complex according to claim 16 .
28. A method for the treatment of disease states associated with osteoporosis, hypercalcemia, cancer induced bone metastasis, Paget's disease or adjuvant or neoadjuvant cancer therapies comprising the step of administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition according to claim 17 .