Compositions for oral administration of zoledronic acid or related compounds for treating complex regional pain syndrome

1. A method of treating complex regional pain syndrome comprising orally administering a dosage form to a human being in need thereof, wherein the dosage form comprises:

a) zoledronic acid which is free of Ion 1 and Ion 2; or

b) one of the following:

1) zoledronic acid and

 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; or

2) zoledronic acid and

 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; or

3) zoledronic acid and a combination of Ion 1 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w, and Ion 2 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w;

wherein the dosage form is free of therapeutically active agents that are not zoledronic acid in a salt form or in an acid form, Ion 1 in a salt form, or Ion 2 in a salt form;

wherein any amount in % w/w is based upon the total weight of zoledronic acid, Ion 1, Ion 2, and any corresponding counter ions;

wherein the bioavailability of zoledronic acid in the dosage form to the human being is about 1.1% to 2.4%; and

wherein oral administration of the dosage form to the human being in a fasted state results in an area under the plasma concentration curve (AUC) of zoledronic acid of about 50 ng·hr/mL to about 500 ng·hr/mL, measured over a 24-hour period.

2. The method of claim 1 , wherein the zoledronic acid is in a disodium salt form.

3. The method of claim 1 , wherein the bioavailability of zoledronic acid in the dosage form to the human being is about 1.1% to 2.3%.

4. The method of claim 1 , wherein oral administration of the dosage form to the human being in a fasted state results in an AUC of zoledronic acid of about 100 ng·hr/mL to about 200 ng·hr/mL, measured over a 24-hour period.

5. The method of claim 1 , wherein oral administration of the dosage form to the human being in a fasted state results in an AUC of zoledronic acid of about 200 ng·hr/mL to about 300 ng·hr/mL, measured over a 24-hour period.

6. The method of claim 1 , wherein oral administration of the dosage form to the human being in a fasted state results in an AUC of zoledronic acid of about 300 ng·hr/mL to about 400 ng·hr/mL, measured over a 24-hour period.

7. The method of claim 1 , wherein oral administration of the dosage form to the human being in a fasted state results in an AUC of zoledronic acid of about 400 ng·hr/mL to about 500 ng·hr/mL, measured over a 24-hour period.

8. The method of claim 1 , wherein the dosage form contains about 40 mg to about 150 mg of the zoledronic acid.

9. The method of claim 2 , wherein the dosage form contains about 50 mg to about 200 mg of the zoledronic acid in the disodium salt form.

10. The method of claim 1 , wherein the dosage form contains about 150 mg to about 200 mg of the zoledronic acid.

11. The method of claim 2 , wherein the dosage form contains about 50 mg to about 60 mg of the zoledronic acid in the disodium salt form.

12. The method of claim 2 , wherein the dosage form contains about 150 mg to about 200 mg of the zoledronic acid in the disodium salt form.

13. The method of claim 1 , wherein the dosage form is orally administered daily, weekly, biweekly, monthly, every two or three months, once a year, or twice a year.

14. The method of claim 11 , wherein the dosage form is orally administered weekly for 6 weeks.

15. The method of claim 12 , wherein the dosage form is orally administered biweekly 3 times within a period of about one month.

16. The method of claim 11 , wherein oral administration of the dosage form to the human being in a fasted state results in a C max of zoledronic acid of about 30 ng/mL to about 40 ng/mL.

17. The method of claim 1 , wherein oral administration of the dosage form to the human being in a fasted state results in a C max of zoledronic acid of about 20 ng/mL to about 50 ng/mL.

18. A dosage form comprising:

a) zoledronic acid which is free of Ion 1 and Ion 2; or

b) one of the following:

1) zoledronic acid and

 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; or

2) zoledronic acid and

 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; or

3) zoledronic acid and a combination of Ion 1 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w, and Ion 2 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w;

wherein the dosage form is free of therapeutically active agents that are not zoledronic acid in a salt form or in an acid form, Ion 1 in a salt form, or Ion 2 in a salt form;

wherein any amount in % w/w is based upon the total weight of zoledronic acid, Ion 1, Ion 2, and any corresponding counter ions;

wherein the bioavailability of zoledronic acid in the dosage form to a human being is about 1.1% to 2.4%; and

wherein oral administration of the dosage form to the human being in a fasted state results in an area under the plasma concentration curve (AUC) of zoledronic acid of about 50 ng·hr/mL to about 500 ng·hr/mL, measured over a 24-hour period.

19. The dosage form of claim 18 , wherein oral administration of the dosage form to the human being in a fasted state results in an AUC of zoledronic acid of about 130 ng·hr/mL to about 180 ng·hr/mL, measured over a 24-hour period.

20. The dosage form of claim 18 , wherein the bioavailability of zoledronic acid in the dosage form to the human being is about 1.2% to 2.2%.

21. The dosage form of claim 18 , wherein oral administration of the dosage form to the human being in a fasted state results in an AUC of zoledronic acid of about 130 ng·hr/mL to about 140 ng·hr/mL, measured over a 24-hour period.

22. The dosage form of claim 18 , wherein oral administration of the dosage form to the human being in a fasted state results in an AUC of zoledronic acid of about 140 ng·hr/mL to about 150 ng·hr/mL, measured over a 24-hour period.

23. The dosage form of claim 18 , wherein oral administration of the dosage form to the human being in a fasted state results in an AUC of zoledronic acid of about 150 ng·hr/mL to about 200 ng·hr/mL, measured over a 24-hour period.

24. The dosage form of claim 18 , wherein oral administration of the dosage form to the human being in a fasted state results in an AUC of zoledronic acid of about 250 ng·hr/mL to about 300 ng·hr/mL, measured over a 24-hour period.

25. The dosage form of claim 18 , wherein oral administration of the dosage form to the human being in a fasted state results in an AUC of zoledronic acid of about 300 ng·hr/mL to about 350 ng·hr/mL, measured over a 24-hour period.

26. The dosage form of claim 18 , wherein oral administration of the dosage form to the human being in a fasted state results in an AUC of zoledronic acid of about 350 ng·hr/mL to about 400 ng·hr/mL, measured over a 24-hour period.

27. The dosage form of claim 18 , wherein oral administration of the dosage form to the human being in a fasted state results in an AUC of zoledronic acid of about 400 ng·hr/mL to about 500 ng·hr/mL, measured over a 24-hour period.

28. The dosage form of claim 18 , wherein the dosage form contains about 50 mg to about 200 mg of the zoledronic acid.

29. The dosage form of claim 18 , wherein the dosage form contains about 50 mg to about 60 mg of the zoledronic acid in a disodium salt form.

30. The dosage form of claim 18 , wherein the dosage form contains about 100 mg to about 200 mg of the zoledronic acid in an acid form or a salt form.