Formulations Of Low Dose Diclofenac And Beta-Cyclodextrin

Abstract

The present invention is directed to a pharmaceutical composition containing a unit dose of a diclofenac compound effective to induce analgesia; and a beta-cyclodextrin compound; wherein the dose of the diclofenac compound is less than 10 mg. The present invention is also directed to methods of treating a subject in need of analgesia with the pharmaceutical compositions of the invention.

Description

DESCRIPTION OF THE FIGURES

FIG. 1 contains a graphical representation of the 100 mm visual analog pain relief (mm) afforded to patients over time (hours) based on the formulation strengths administered. The tested formulations include placebo, 3.75 mg Dyloject, 9.4 mg Dyloject, 18.75 mg Dyloject; 37.5 mg Dyloject, 75 mg Dyloject, and 30 mg Ketorolac.

FIG. 2 illustrates the dose-response curve for peak analgesia observed (mm VAS) over mg of formulation. Both diclofenac and ketorolac formulations were tested.

FIG. 3 illustrates the dose-duration relationship examined using the median time to re-medication (hours) in the single dose phase. Two formulations of diclofenac were studied.

FIG. 4 illustrates the percentage of patients with NSAID Adverse Events by dose of diclofenac (mg).

Claims

1. A pharmaceutical composition comprising: (a) a unit dose of a diclofenac compound effective to induce analgesia; and(b) a beta-cyclodextrin compound;wherein the dose of the diclofenac compound is less than 10 mg.

2. The pharmaceutical composition of claim 1, wherein the diclofenac compound is a diclofenac salt.

3. The pharmaceutical composition of claim 2, wherein the diclofenac salt is diclofenac sodium.

4. The pharmaceutical composition of claim 1, wherein the cyclodextrin compound is 2-hydroxypropyl-beta-cyclodextrin.

5. The pharmaceutical composition of claim 1, further comprising a stabilizer.

6. The pharmaceutical composition of claim 5, wherein the stabilizer is monothioglycerol.

7. The pharmaceutical composition of claim 1, wherein the dose of diclofenac is about 9.4 mg.

8. The pharmaceutical composition of claim 1, wherein the dose of diclofenac is less than about 5 mg.

9. The pharmaceutical composition of claim 8, wherein the dose of diclofenac is about 3.75 mg.

10. A method for treating a mammal in need of analgesia, which comprises administering the pharmaceutical composition of claim 1.

11. The method of claim 10, wherein the diclofenac compound is diclofenac sodium.

12. A method for treating a mammal in need of an analgesia, which comprises administering the pharmaceutical composition of claim 8.

13. The method of claim 12, wherein the diclofenac compound is diclofenac sodium.

14. The method of claim 11, wherein the pharmaceutical composition is administered intravenously.

15. The method of claim 13, wherein the pharmaceutical composition is administered intravenously.

16. A method for treating a mammal in need of analgesia, which comprises administering a pharmaceutical composition comprising: (a) a dosage of a diclofenac compound effective to induce analgesia; and(b) a beta-cyclodextrin compound;wherein the dosage of the diclofenac compound is less than about 1.3 mg/kg per day.

17. The method of claim 16, wherein the dosage of diclofenac is less than 0.65 mg/kg per day.

18. The method of claim 17, wherein the dosage of diclofenac is less than 0.33 mg/kg per day.

19. The method of claim 18, wherein the dosage of diclofenac is less than 0.165 mg/kg per day.

20. The method of claim 16, wherein the diclofenac compound is diclofenac sodium.

21. A method for treating a mammal in need of analgesia, which comprises administering a pharmaceutical composition comprising: (a) a dosage of a diclofenac compound effective to induce analgesia; and(b) a beta-cyclodextrin compound;wherein the dosage of the diclofenac compound is less than a minimum approved dose for the route of administration.

22. The method of claim 21, wherein a dose of the diclofenac compound has the same efficacy of pain relief as the minimum approved dose.

23. The method of claim 21, wherein the dose of the diclofenac compound has from about 70% to about 100% of the efficacy of pain relief as the minimum approved dose.

24. The method of claim 21, wherein the dose of the diclofenac compound has from about 40% to about 70% of the efficacy of pain relief as the minimum approved dose.

25. The method of claim 21, wherein the dose of the diclofenac compound has the same duration of pain relief as the minimum approved dose.

26. The method of claim 21, wherein the dose of the diclofenac compound has from about two-thirds to the same duration of pain relief as the minimum approved dose.

27. The method of claim 21, wherein the dose of the diclofenac compound has about one-third to about two-thirds of the duration of pain relief as the minimum approved dose.