Formulations Of Low Dose Non-Steroidal Anti-Inflammatory Drugs And Beta-Cyclodextrin

Abstract

The present invention is directed to pharmaceutical compositions containing (a) a dosage of a non-steroidal anti-inflammatory drug (NSAID) effective to induce analgesia an anti-inflammatory effect, or an anti-pyretic effect and (b) a beta-cyclodextrin compound; wherein the dosage of the NSAID compound is less than the minimum approved dose for the route of administration. Additionally, the present invention is directed to methods for treating a mammal in need of an analgesic, an anti-inflammatory, or an anti-pyretic agent comprising administering the pharmaceutical composition of the present 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 dosage of a non-steroidal anti-inflammatory drug (NSAID) effective to induce analgesia an anti-inflammatory effect, or an anti-pyretic effect and (b) a beta-cyclodextrin compound;wherein the dosage of the NSAID compound is less than the minimum approved dose for the route of administration.

2. The pharmaceutical composition of claim 1, wherein the dosage of the NSAID is less than about 50% of the minimum approved dose for the route of administration.

3. The pharmaceutical composition of claim 2, wherein the dosage of the NSAID is less than about 25% of the minimum approved dose for the route of administration.

4. The pharmaceutical composition of claim 1, wherein the NSAID is diflunisal, indomethacin, sulindac, etodolac, mefenamic acid, meclofenamate, flufenamic acid, tolmetin, ketorolac, diclofenac, ibuprofen, naproxen, fenoprofen, ketoprofen, flurbiprofen, oxaprozin, piroxicam, meloxicam, nabumetone, celecoxib, valdecoxib, parecoxib, etoricoxib or lumaricoxib.

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

6. A method for treating a mammal in need of an analgesic, an anti-inflammatory, or an anti-pyretic agent comprising administering the pharmaceutical composition of claim 1.

7. The method for treating a mammal according to claim 6, wherein the pharmaceutical composition is administered intramuscularly.

8. The method for treating a mammal according to claim 6, wherein the pharmaceutical composition is administered intravenously.

9. A method for treating a mammal in need of an analgesic, an anti-inflammatory, or an anti-pyretic agent, which comprises administering a pharmaceutical composition comprising: (a) a dosage of an NSAID effective to induce analgesia an anti-inflammatory effect, or an anti-pyretic effect; and(b) a beta-cyclodextrin compound;wherein the dosage of the NSAID is less than the minimum approved dose for the route of administration.

10. The method of claim 9, wherein the NSAID is diflunisal, indomethacin, sulindac, etodolac, mefenamic acid, meclofenamate, flufenamic acid, tolmetin, ketorolac, diclofenac, ibuprofen, naproxen, fenoprofen, ketoprofen, flurbiprofen, oxaprozin, piroxicam, meloxicam, nabumetone, celecoxib, valdecoxib, parecoxib, etoricoxib or lumaricoxib.

11. The method of claim 9, wherein the dose of the NSAID has the same efficacy as the minimum approved dosage.

12. The method of claim 9, wherein the dose of the NSAID has from about 70% to about 100% of the efficacy of the minimum approved dosage.

13. The method of claim 9, wherein the dosage of the NSAID has from about 40% to about 70% of the efficacy of the minimum approved dosage.

14. The method of claim 9, wherein the dosage of the NSAID has the same duration as the minimum approved dosage.

15. The method of claim 9, wherein the dosage of the NSAID has from about two-thirds to the same duration as the minimum approved dosage.

16. The method of claim 9, wherein the dosage of the NSAID has about one-third to about two-thirds of the duration as the minimum approved dosage.