Pharmaceutical compositions comprising fesoterodine
The present application relates to a pharmaceutical granulate comprising Fesoterodine or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable stabilizer, which can be selected from the group consisting of sorbitol, xylitol, polydextrose, isomalt, dextrose, and combinations thereof, and is preferably a sugar alcohol selected from the group consisting of xylitol and sorbitol. The granulate is suitable for incorporation into pharmaceutical compositions comprising a gel matrix formed by at least one type of hydroxypropyl methylcellulose into which the Fesoterodine is embedded and, optionally, further excipients. In certain embodiments, the granulate is formed by a process of wet granulation.
1. A pharmaceutical composition comprising Fesoterodine, or a pharmaceutically acceptable salt, and xylitol, where the ratio of Fesoterodine/xylitol is about 1-20% [w/w].
2. A pharmaceutical composition according to claim 1 , which comprises a salt of Fesoterodine which has an auto pH in water of 3-5.
3. A pharmaceutical composition according to claim 2 , wherein the Fesoterodine salt is a salt of a di- or tricarboxylic acid, or of a partially hydrogenated di- or tricarboxylic acid.
4. A pharmaceutical composition according to claim 3 , which comprises Fesoterodine hydrogen fumarate.
5. A pharmaceutical composition according to claim 4 , which is in unit dosage form and characterized in that Fesoterodine hydrogen fumarate is present in an amount of between 0.5 and 12 mg per dosage unit.
6. A pharmaceutical composition according to claim 1 , which is obtainable by a method involving at least one granulation step.
7. A pharmaceutical composition according to claim 6 , wherein the granulation is wet granulation.
8. A pharmaceutical composition according to claim 7 , wherein the granulation is performed in the presence of water.
9. A pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition further comprises a sustained release agent.
10. A pharmaceutical composition according to claim 9 , wherein the sustained release agent is a cellulose ether or ester or a mixture thereof.
11. A pharmaceutical composition according to claim 10 , wherein the sustained release agent is hydroxypropylmethylcellulose.
12. A pharmaceutical composition according to claim 9 , wherein the sustained release agent is contained in an amount of about 20-80% [w/w], based on the total composition.
13. A pharmaceutical composition according to claim 9 , which exhibits a cumulated Fesoterodine release (in weight percent based on the theoretical amount of Fesoterodine in the formulation) in an in vitro dissolution assay according to USP 711 (in phosphate buffer pH 6.8, 37° C., at 75 rpm) as follows:
about 5% to about 30% Fesoterodine release after 1 hour,
about 15% to about 40% Fesoterodine release after 2 hours,
about 35% to about 65% Fesoterodine release after 4 hours, and
at least about 75% Fesoterodine release after 16 hours.
14. The pharmaceutical composition according to claim 1 , wherein the Fesoterodine/xylitol ratio [w/w] is about 3-15%.
15. A pharmaceutical composition according to claim 1 , wherein the Fesoterodine/xylitol ratio [w/w] is about 5-10%.
16. A pharmaceutical composition according to claim 14 , comprising a salt of Fesoterodine, wherein the Fesoterodine salt is a salt of a di- or tricarboxylic acid, or of a partially hydrogenated di- or tricarboxylic acid.
17. A pharmaceutical composition according to claim 16 , which comprises Fesoterodine hydrogen fumarate.
18. A pharmaceutical composition according to claim 1 , wherein the Fesoterodine/xylitol ratio [w/w] is about 11%.
19. The pharmaceutical composition according to claim 12 , wherein the sustained release agent is contained in an amount of about 25-65%, based on the total composition.
20. The pharmaceutical composition according to claim 12 , wherein the sustained release agent is contained in an amount of about 30-65%, based on the total composition.
21. The pharmaceutical composition according to claim 12 , wherein the sustained release agent is contained in an amount of about 35-55%, based on the total composition.
22. The pharmaceutical composition according to claim 13 , which exhibits a cumulated Fesoterodine release (in weight percent based on the theoretical amount of Fesoterodine in the formulation) in an in vitro dissolution assay according to USP 711 (in phosphate buffer pH 6.8, 37° C., at 75 rpm) as follows:
about 6% to about 26% Fesoterodine release after 1 hour,
about 18% to about 38% Fesoterodine release after 2 hours,
about 36% to about 56% Fesoterodine release after 4 hours, and
at least about 80% Fesoterodine release after 16 hours.