Pharmaceutical compositions comprising meloxicam
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, solubility, or pharmacokinetics of the drug for the treatment of conditions such as pain.
1. A method of dissolving a combination of meloxicam and rizatriptan in a stomach of a human being, comprising orally administering, to the human being, a solid oral dosage form comprising: a complex of meloxicam with a sulfobutyl ether β-cyclodextrin (SBEβCD), 400 mg to 800 mg of a bicarbonate, and rizatriptan, wherein the dosage form has improved dissolution of meloxicam as compared to a reference dosage form containing: 1) the same amount of meloxicam, and 2) no bicarbonate, wherein the improved dissolution of meloxicam is determined by the following test: adding the dosage form or the reference dosage form to 500 mL of a 0.01 N HCl aqueous solution, stirring at 75 revolutions per minute (RPM) with a USP paddle apparatus II at 37° C., and determining the amount of meloxicam dissolved in the 0.01 N HCl aqueous solution after 15 minutes.
2. The method of claim 1 , wherein about 8 mg to about 13 mg of the rizatriptan is present in the dosage form based upon the weight of the rizatriptan in the free base form.
3. The method of claim 2 , wherein the rizatriptan is present in a salt form in an amount that is a molar equivalent to 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 dosage form contains about 15 mg to about 25 mg of meloxicam.
6. The method of claim 5 , wherein the dosage form contains about 20 mg of meloxicam.
7. The method of claim 1 , wherein the dosage form contains about 100 mg to about 175 mg of the SBEβCD.
8. The method of claim 1 , wherein the dosage form contains about 100 mg to about 140 mg of the SBEβCD.
9. The method of claim 1 , wherein the bicarbonate comprises sodium bicarbonate.
10. The method of claim 1 , wherein the dosage form contains about 450 mg to about 550 mg of the bicarbonate.
11. The method of claim 1 , wherein the dosage form contains about 500 mg of sodium bicarbonate.
12. The method of claim 1 , wherein the bicarbonate improves solubility of meloxicam in the dosage form in a greater extent than a carbonate would in a reference dosage form containing: (1) about same amount of meloxicam, (2) an amount of a carbonate that would achieve same pH as the bicarbonate, and (3) no bicarbonate.
13. The method of claim 1 , wherein the dosage form is orally administered to the human being to treat migraine.
14. The method of claim 13 , wherein the human being has had an inadequate response to a prior treatment for migraine.
15. The method of claim 1 , wherein the human being experiences pain relief sooner than would be experienced as a result of orally administering the reference dosage form containing: 1) the same amount of meloxicam, and 2) no bicarbonate.
16. The method of claim 1 , wherein the dosage form has a rizatriptan solubility property that, as a result of adding the dosage form to 500 mL of a 0.01 N HCl aqueous solution, stirring at 75 revolutions per minute (RPM) with a USP paddle apparatus II at 37° C., and determining the amount of rizatriptan dissolved in the 0.01 N HCl aqueous solution after 15 minutes, at least about 50% of the rizatriptan in the dosage form is dissolved in the 0.01 N HCl aqueous solution.
17. The method of claim 1 , wherein the meloxicam and the rizatriptan have a molar ratio of about 1 to about 2.
18. The method of claim 1 , wherein the T max of meloxicam in the dosage form is less than about 2 hours.
19. The method of claim 1 , wherein the T max of meloxicam in the dosage form is less than about 3 hours.