Stable pharmaceutical formulations of montelukast sodium

Abstract

The invention encompasses stable pharmaceutical compositions comprising montelukast or salts thereof and methods of preparing the same.

Description

Claims

1. A stable montelukast pharmaceutical composition comprising montelukast or a salt thereof and a pharmaceutically acceptable excipient, wherein the pharmaceutically acceptable excipient is present in an amount that does not increase the amount of the corresponding sulfoxide of montelukast in the composition to exceed 1% by weight of the initial amount of montelukast after the composition has been stored at about 55° C. for 48 hours.

2. The pharmaceutical composition according to claim 1, wherein the salt is montelukast sodium and the corresponding sulfoxide is the sulfoxide of formula (I).

3. The pharmaceutical composition according to claim 1, wherein the amount of the corresponding sulfoxide does not exceed more than 0.73% by weight of the initial amount of montelukast after storage.

4. The pharmaceutical composition according to claim 1, wherein the amount of the corresponding sulfoxide does not exceed more than 0.57% by weight of the initial amount of montelukast after storage.

5. The pharmaceutical composition according to claim 4, wherein the composition is in a solid dosage form.

6. The pharmaceutical composition according to claim 5, wherein the solid dosage form is a tablet or a capsule.

7. A film coated tablet comprising the pharmaceutical composition of claim 1 and a coating agent.

8. The film coated tablet according to claim 7, comprising montelukast sodium, lactose monohydrate, hydroxypropylcellulose, starch, sodium starch glycolate, magnesium stearate, and a coating agent.

9. A chewable tablet comprising the pharmaceutical composition of claim 1.

10. The chewable tablet according to claim 9 comprising montelukast sodium, hydroxypropylcellulose, sodium starch glycolate, mannitol, color iron oxide, aspartame, flavoring agent, and magnesium stearate.

11. The chewable tablet according to claim 10 further comprising sodium lauryl sulfate.

12. A process for preparing the pharmaceutical composition of claim 1 comprising combining montelukast or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable excipient, wherein the pharmaceutically acceptable excipient is present in an amount that does not increase the amount of the corresponding sulfoxide of montelukast in the composition to exceed 1% by weight of the initial amount of montelukast after the composition has been stored at about 55° C. for 48 hours.

13. The process according to claim 12, wherein the pharmaceutical composition is prepared by wet granulation.

14. The process according to claim 12, comprising blending montelukast sodium, lactose monohydrate, hydroxypropylcellulose, starch, sodium lauryl sulfate, sodium starch glycolate and magnesium stearate in a dry mixing method and compressing the blended components into tablet form.

15. The process according to claim 12 comprising preparing a mixture of montelukast sodium, hydroxypropylcellulose, sodium starch glycolate, mannitol, color iron oxide, aspartame, sodium lauryl sulfate and flavoring agent; granulating the mixture in a wet granulation method; blending the granulated mixture with magnesium stearate to form a blend; and compressing the blend into a chewable tablet.

16. A stable montelukast pharmaceutical composition comprising montelukast or a salt thereof and at least one pharmaceutically acceptable excipient, wherein the pharmaceutically acceptable excipient is chosen by: a) providing a mixture of montelukast and a pharmaceutically acceptable excipient wherein the pharmaceutically acceptable excipient is present in an amount that does not increase the amount of the corresponding sulfoxide of montelukast in the composition to exceed 1% by weight of the initial amount of montelukast after the composition has been stored at about 55° C. for 48 hours;b) storing the mixture at 55° C. for 48 hours;c) determining the presence and amount of a montelukast sulfoxide in the mixture; andc) selecting the pharmaceutically acceptable excipient that does not increase the amount of the corresponding sulfoxide of montelukast in the mixture to exceed 1% by weight of the initial amount of montelukast in the mixture.