Pharmaceutical compositions comprising meloxicam
View Patent ↗Disclosed herein are compositions comprising a drug such as a triptan (e.g. rizatriptan) and/or an NSAID (e.g. meloxicam) in combination with a cyclodextrin and/or a carbonate or a bicarbonate. These compositions may be orally administered, for example, to improve the bioavailability or pharmacokinetics of the drug for the treatment of conditions such as pain.
1. A method of treating migraine comprising: orally administering a dosage form to a human being suffering from migraine, wherein the dosage form comprises a combination of: 1) a complex of meloxicam with a sulfobutyl ether β-cyclodextrin (SBEβCD), 2) a bicarbonate, and 3) a rizatriptan; wherein the dosage form contains 400 mg to 600 mg of the bicarbonate, about 5 mg to about 50 mg of meloxicam, and about 50 mg to about 200 mg of the SBEβCD; wherein the dosage form is a solid oral dosage form having a shorter T max of meloxicam in the human being than a reference dosage form that: 1) contains the same amount of meloxicam, 2) does not contain an SBEβCD, and 3) does not contain a bicarbonate; and wherein the human being experiences more pain relief at two hours after the dosage form is administered as compared to: a) the pain relief that the human being would have experienced two hours after receiving a first reference dosage form containing the same amount of meloxicam without the rizatriptan, and b) the pain relief that the human being would have experienced two hours after receiving a second reference dosage form containing the same amount of the rizatriptan without meloxicam.
2. The method of claim 1 , wherein about 1 mg to about 50 mg of the rizatriptan is present in the oral dosage form based upon the weight of the rizatriptan in the free base form.
3. The method of claim 1 , wherein the rizatriptan is present in a salt form in an amount that is a molar equivalent of about 10 mg of the rizatriptan in the free base form.
4. The method of claim 3 , wherein the rizatriptan is present as rizatriptan benzoate.
5. The method of claim 1 , wherein the oral dosage form contains about 10 mg to about 30 mg of meloxicam.
6. The method of claim 1 , wherein the oral dosage form contains about 20 mg of meloxicam.
7. The method of claim 1 , wherein the oral dosage form contains about 15 mg of meloxicam.
8. The method of claim 1 , wherein the SBEβCD has about 6 to about 7 sulfobutyl ether groups for each molecule of β-cyclodextrin.
9. The method of claim 1 , wherein the SBEβCD has about 6 sulfobutyl ether groups for each molecule of β-cyclodextrin.
10. The method of claim 1 , wherein the SBEβCD has about 7 sulfobutyl ether groups for each molecule of β-cyclodextrin.
11. The method of claim 1 , wherein the oral dosage form contains about 50 mg to about 150 mg of the SBEβCD.
12. The method of claim 1 , wherein the oral dosage form contains about 100 mg of the SBEβCD.
13. The method of claim 1 , wherein the molar ratio of the SBEβCD to meloxicam is about 0.5 to about 2.
14. The method of claim 1 , wherein the molar ratio of the SBEβCD to meloxicam is about 0.8 to about 1.2.
15. The method of claim 1 , wherein the molar ratio of the SBEβCD to meloxicam is about 1.
16. The method of claim 1 , wherein the oral dosage form contains about 10 mg to about 40 mg of meloxicam, and about 5 mg to about 50 mg of rizatriptan.
17. The method of claim 1 , wherein the oral dosage form contains SBEβCD that is in a weight ratio to rizatriptan that is within a range of about 1 to about 100.
18. The method of claim 17 , wherein the oral dosage form contains SBEβCD that is in a weight ratio to rizatriptan that is about 10.
19. The method of claim 17 , wherein the oral dosage form contains about 20 mg of meloxicam.
20. The method of claim 1 , wherein the bicarbonate comprises sodium bicarbonate.
21. The method of claim 20 , wherein the oral dosage form contains 500 mg of sodium bicarbonate.
22. The method of claim 1 , wherein the oral dosage form has been shown to have a median T max of meloxicam that is less than about 90 minutes in fasted human subjects.
23. The method of claim 1 , wherein the oral dosage form has been shown to have a median T max of meloxicam that is less than about 2 hours in fasted human subjects.
24. The method of claim 1 , wherein the oral dosage form has been shown to have faster time to therapeutic plasma concentration in the human being as compared to the reference dosage form.