You’re using a public version of DrugPatentWatch with 5 free searches available | Register to unlock more free searches. CREATE FREE ACCOUNT

Last Updated: March 29, 2024

Claims for Patent: 5,356,896


✉ Email this page to a colleague

« Back to Dashboard


Summary for Patent: 5,356,896
Title: Stabilized pharmaceutical compositions comprising an HMG-CoA reductase inhibitor compound
Abstract:A pharmaceutical dosage form comprising an HMG-CoA reductase inhibitor compound, e.g., fluvastatin sodium, is disclosed which is stabilized against pH-related degradation by an alkaline stabilizing medium capable of imparting a pH of at least 8 to an aqueous solution or dispersion of the composition.
Inventor(s): Kabadi; Mohan B. (Marlboro, NJ), Vivilecchia; Richard V. (Rockaway, NJ)
Assignee: Sandoz Ltd. (Basel, CH)
Application Number:07/995,252
Patent Claims: 1. A pharmaceutical composition comprising an HMG-CoA reductase inhibitor compound of the formula: ##STR4## wherein R is an organic radical,

X is --CH.dbd.CH--, and

M is a physiologically acceptable cation,

and an alkaline stabilizing medium capable of imparting a pH of at least 8 to an aqueous solution or dispersion of the composition wherein the alkaline stabilizing medium comprises at least one pharmaceutically acceptable carbonate salt.

2. A pharmaceutical composition according to claim 1 wherein R is selected from the group consisting of indolyl, pyrimidinyl, indenyl, pyridinyl and quinolinyl radicals and derivatives thereof, and X is (E)--CH.dbd.CH--.

3. A pharmaceutical composition according to claims 2 wherein the pharmaceutically acceptable carbonate salt is selected from the group consisting of sodium carbonate, sodium bicarbonate, calcium carbonate and mixtures thereof.

4. A pharmaceutical composition according to claim 1 wherein the alkaline stabilizing medium comprises a mixture of a water soluble carbonate and a water insoluble or sparingly soluble carbonate.

5. A pharmaceutical composition according to claim 4 wherein the ratio of water soluble carbonate to water insoluble or sparingly soluble carbonate is from 1:40 to 2:1.

6. A pharmaceutical composition comprising the HMG-CoA reductase inhibitor fluvastatin sodium and a pharmaceutically acceptable alkaline stabilizing medium capable of imparting a pH of at least 8 to an aqueous solution or dispersion of the composition.

7. A pharmaceutical composition according to claim 6 wherein the alkaline stabilizing medium comprises at least one pharmaceutically acceptable carbonate salt.

8. A pharmaceutical composition according to claim 7 wherein the pharmaceutically acceptable carbonate salt is selected from the group consisting of sodium carbonate, sodium bicarbonate, calcium carbonate and mixtures thereof.

9. A pharmaceutical composition according to claim 8 comprising fluvastatin sodium, (i) calcium carbonate and (ii) sodium carbonate or sodium bicarbonate.

10. A pharmaceutical composition according to claims 1, 3, or 8 which comprises 0.5 to 60 wt. % HMG-CoA reductase inhibitor compound, 0.5 to 40 wt. % calcium carbonate, 0.5 to 20 wt. % sodium bicarbonate, and 10 to 65 wt. % microcrystalline cellulose.

11. A pharmaceutical composition according to claims 2 or 6 in solid unit dosage form.

12. An oral pharmaceutical composition suitable for excapsulation for delivering fluvastatin sodium which comprises 0.5 to 60 wt. % of fluvastatin sodium,

25 to 40 wt. % of calcium carbonate,

0.5 to 10 wt. % of sodium bicarbonate, and

20 to 35 wt. % of microcrystalline cellulose.

13. An oral pharmaceutical composition suitable for tableting for delivering fluvastatin sodium which comprises

0.5 to 60 wt. % of fluvastatin sodium,

5 to 20 wt. % of calcium carbonate,

5 to 20 wt. % of sodium bicarbonate, and

50 to 65 wt. % of microcrystalline cellulose.

14. A composition according to claim 12 wherein the capsule is coated with an enteric and/or film coating.

15. A composition according to claim 13 wherein the tablet is coated with an enteric and/or film coating.

16. A composition according to claim 12 wherein fluvastatin sodium is present in a dosage amount selected from the group consisting of 5, 10, 15, 20 and 40 mg. amounts.

17. A composition according to claim 13 wherein fluvastatin sodium is present in a dosage amount selected from the group consisting of 5, 10, 15, 20 and 40 mg. amounts.

18. A composition according to claims 2 or 8 wherein the HMG-CoA reductase inhibitor compound and the pharmaceutically acceptable carbonate salt are in intimate contacting association.

19. A method of preparing the composition of claims 2 or 8 which comprises bringing the HMG-CoA reductase inhibitor compound and the alkaline stabilizing medium into intimate contacting association by co-lyophilizing the HMG-CoA reductase inhibitor compound and the alkaline stabilizing medium.

20. A pharmaceutical composition according to claim 2 wherein the HMG-CoA reductase inhibitor compound is a pharmaceutically acceptable salt of erythro-3R,5S-(E)-7-[4-fluorophenyl-6-(1-methylethyl)-2-(dimethylamino-pyr imidin-5-yl)-3,5-dihydroxy-6-heptenoic acid, or its racemate.

21. A pharmaceutical composition according to claim 2 wherein the HMG-CoA reductase inhibitor compound is a pharmaceutically acceptable salt of erythro-3R,5S-(E)-dimethoxy-7-[3'-(4"-fluorophenyl)-spiro[cyclopentane-1,1 '(1H)-inden]-2'-yl]-3-hydroxyhept-6-enoic acid, or racemate.

22. A pharmaceutical composition according to claim 2 wherein the HMG-CoA reductase inhibitor compound is a pharmaceutically acceptable salt of erythro-3R,5S-(E)-7-[4-(4-fluorophenyl)-2,6-bis(1-methylethyl)-5-methoxyme thyl-pyridin-3-yl]-3,5-dihydroxy-6-heptenoic acid, or its racemate.

23. A pharmaceutical composition according to claim 2 wherein the HMG-CoA reductase inhibitor compound is a pharmaceutically acceptable salt of erythro-(.+-.)-(E)-[4-(4-fluorophenyl)-2-(1-methylethyl)-6-phenyl-pyridin- 3-yl]-3,5- dihydroxy-6-heptenoic acid, or its 3R,5S isomer.

24. A pharmaceutical composition according to claim 2 wherein the HMG-CoA reductase inhibitor compound is a pharmaceutically acceptable salt of erythro-(.+-.)-(E)-7-[4-(4-fluorophenyl)-2-(1-methylethyl)-quinolin-3-yl]- 3,5-dihydroxy-6- heptenoic acid, or its 3R,5S isomer.

25. A pharmaceutical composition according to claim 2 wherein the HMG-CoA reductase inhibitor compound is a pharmaceutically acceptable salt of erythro-(.+-.)-(E)-7-[4-(4-fluorophenyl)-2-cyclopropyl-quinolin-3-yl]-3,5- dihydroxy-6-heptenoic acid, or its 3R, 5S isomer.

26. A pharmaceutical composition according to claim 2 which comprises erythro-(E)-3R,5S-7-[3-(4-fluorophenyl)-1-(1-methylethyl)-1H-indol-2-yl]-3 ,5-dihydroxy-6-heptenoic acid, sodium salt.

27. A pharmaceutical composition according to claims 2 or 7 which comprises 0.5 to 60 wt. % HMG-CoA reductase compound, 10 to 55 wt. % pharmaceutically acceptable carbonate salts, and 10 to 65 wt. % filler.

Make Better Decisions: Try a trial or see plans & pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.