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
(a) about 0.3-5.0% [w/w] of a pharmaceutically acceptable salt of fesoterodine
(b) about 5-25% [w/w] of xylitol or sorbitol,
(c) about 20-40% [w/w] of a mixture comprising about 45-80% [w/w] lactose monohydrate and about 20-55% [w/w] microcrystalline cellulose;
(d) about 20-80% [w/w] hydroxypropyl methylcellulose; and
(e) about 1-10% [w/w] lubricants.
2. The pharmaceutical composition of claim 1 , comprising
(a) about 4.0 mg fesoterodine hydrogen fumarate
(b) about 32-40 mg of xylitol with a mean particle size of about 0.001-0.30 mm
(c) about 115-130 mg of a mixture of lactose monohydrate and microcrystalline cellulose
(d) about 65-75 mg of HPMC (hydroxypropyl methylcellulose) having a nominal viscosity of about 100,000 mPa·s when dissolved (about 2% by weight) in water
(e) about 65-75 mg of HPMC having a nominal viscosity of about 4,000 mPa·s when dissolved (about 2% by weight) in water
(f) about 8-12 mg of glycerol dibehenate, and
(g) about 7-10 mg talc.
3. The pharmaceutical composition of claim 1 , comprising
(a) about 8.0 mg fesoterodine hydrogen fumarate
(b) about 65-80 mg of xylitol with a mean particle size of about 0.001-0.30 mm
(c) about 70-85 mg of a mixture of lactose monohydrate and microcrystalline cellulose
(d) about 110-130 mg of HPMC having a nominal viscosity of about 100,000 mPa·s when dissolved (about 2% by weight) in water
(e) about 20-30 mg of HPMC having a nominal viscosity of about 4,000 mPa·s when dissolved (about 2% by weight) in water
(f) about 8-12 mg of glycerol dibehenate, and
(g) about 7-10 mg talc.
4. The pharmaceutical composition of claim 1 , comprising
fesoterodine hydrogen fumarate
about 0.5-4.0%
xylitol
about 5-25%
a mixture of lactose monohydrate
about 20-40%
and microcrystalline cellulose
HPMC (high viscosity)
about 15-40%
HPMC (low viscosity)
about 5-25%
glycerol dibehenate
about 1-5%
Talc
about 1-5%.
5. The pharmaceutical composition of claim 1 , comprising
fesoterodine hydrogen fumarate
about 4.0
mg
xylitol
about 36.0
mg
a mixture of lactose monohydrate
about 121.5
mg
and microcrystalline cellulose
HPMC having a nominal viscosity
about 70.0
mg
of about 100,000 mPa · s when
dissolved (about 2% by weight) in
water
HPMC having a nominal viscosity of
about 70.0
mg
about 4,000 mPa · s when dissolved
(about 2% by weight) in water
glycerol dibehenate
about 10.0
mg
talc
about 8.5
mg
and a coating.
6. The pharmaceutical composition of claim 1 , comprising
fesoterodine hydrogen fumarate
about 8.0
mg
xylitol
about 72.0
mg
a mixture of lactose monohydrate
about 77.5
mg
and microcrystalline cellulose
HPMC having a nominal viscosity of about
about 120.0
mg
100,000 mPa · s when dissolved
(about 2% by weight) in water
HPMC having a nominal viscosity of about
about 24.0
mg
4,000 mPa · s when dissolved
(about 2% by weight) in water
glycerol dibehenate
about 10.0
mg
talc
about 8.5
mg
and a coating.
7. A pharmaceutical composition according to any one of claims 2 to 6 , comprising a coating of about 15 mg of a mixture of polyvinyl alcohol, PEG, lecithin, talc, titanium dioxide, and indigo carmine aluminum lake.
8. A method of treating a patient suffering from overactive bladder by administering a therapeutically effective amount of a pharmaceutical composition according to any one of claim 1 or 2 - 6 .
9. A method of treating a patient suffering from overactive bladder by administering a therapeutically effective amount of a pharmaceutical composition according to claim 7 .
10. The method according to claim 8 , wherein the patient has a symptom selected from the group consisting of urinary incontinence, urinary urge incontinence, imperative urinary urge, and increased urinary frequency.
11. The method according to claim 8 , wherein the patient suffers from overactive bladder with a symptom selected from the group consisting of urinary urge incontinence, imperative urinary urge, and increased urinary frequency.
12. The method according to claim 9 , wherein the patient has a symptom selected from the group consisting of urinary incontinence, urinary urge incontinence, imperative urinary urge, and increased urinary frequency.
13. The method according to claim 9 , wherein the patient suffers from overactive bladder with a symptom of urinary urge incontinence, imperative urinary urge, and increased urinary frequency.
14. The pharmaceutical composition of any one of claims 2 - 4 further comprising a pharmaceutically acceptable coating.
15. The pharmaceutical composition of claim 5 where
the xylitol has a mean particle size of about 0.001-0.30 mm.
16. The pharmaceutical composition of claim 6 where
the xylitol has a mean particle size of about 0.001-0.20 mm.