NOVEL PHARMACEUTICAL COMPOSITIONS COMPRISING LEVETIRACETAM
The present invention relates to a pharmaceutical composition comprising levetiracetam as active ingredient, the invention relates specifically to a prolonged release formulation.
1 . A pharmaceutical composition in the form of a tablet comprising, as active ingredient, levetiracetam and, as excipient within the core of the tablet, 5.0 to 59.0% per weight of at least one hydrophilic matrix agent, with respect to the total weight of the core of the tablet.
2 . The pharmaceutical composition according to claim 1 , comprising levetiracetam and a water dispersible, rate controlling polymer as hydrophilic matrix agent.
3 . The pharmaceutical composition according to claim 1 or 2 , wherein the composition is coated.
4 . The pharmaceutical composition according to claim 1 , further coated with a hydrophillic polymer to improve its appearance, wherein said polymer is Opadry™.
5 . The pharmaceutical composition according to claim 1 , comprising 20.0 to 30.0% per weight of hydrophilic matrix agent.
6 . The pharmaceutical composition according to claim 5 , wherein the hydrophilic matrix agent is hydropropyl methylcellulose.
7 . The pharmaceutical composition according to claim 1 , comprising levetiracetam, hydroxypropyl methylcellulose and Povidone.
8 . The pharmaceutical composition according to claim 1 , comprising at least one gliding agent as excipient within the core of the tablet.
9 . The pharmaceutical composition according to claim 8 , comprising 0.3 to 3.0% per weight of gliding agent.
10 . The pharmaceutical composition according to claim 8 or 9 , wherein the gliding agent is anhydrous colloidal silica.
11 . The pharmaceutical composition according to claim 1 , comprising at least one lubricant as excipient within the core of the tablet.
12 . The pharmaceutical composition according to claim 11 , comprising 0.0 to 5.50% per weight of lubricant.
13 . The pharmaceutical composition according to claim 11 or 12 , wherein the lubricant is magnesium stearate.
14 . The pharmaceutical composition according to claim 11 or 12 , wherein the lubricant is macrogol 6000.
15 . The pharmaceutical composition according to claim 1 , comprising at least two lubricants as excipient within the core of the tablet.
16 . The pharmaceutical composition according to claim 15 , wherein the lubricants are magnesium stearate and macrogol 6000.
17 . A pharmaceutical composition according to claim 1 , comprising levetiracetam as active ingredient and
5.0 to 59.0% per weight of hydrophilic matrix agent,
0.3 to 3.0% per weight of gliding agent, and
up to 5.50% per weight of lubricant,
with respect to the total weight of the core of the tablet.
18 . A pharmaceutical composition according to claim 1 , comprising levetiracetam as active ingredient and
5.0 to 59.0% per weight of hydroxypropylmethylcellulose,
to 3.0% per weight of anhydrous colloidal silica,
to 5.0% per weight of polyethylene glycol 6000, and
up to 1.0% per weight of magnesium stearate,
with respect to the total weight of the core of the tablet.
18 . A pharmaceutical composition according to claim 1 , comprising levetiracetam as active ingredient and
8.0 to 50.0% per weight of hydrophilic matrix agent,
0.3 to 2.5% per weight of gliding agent, and
up to 3.5% per weight of lubricant,
with respect to the total weight of the core of the tablet.
19 . A pharmaceutical composition according to claim 1 , comprising levetiracetam as active ingredient and
15.0 to 40.0% per weight of hydrophilic matrix agent,
0.4 to 2.0% per weight of gliding agent, and
0.4 to 1.30% per weight of lubricant,
with respect to the total weight of the core of the tablet.
20 . A pharmaceutical composition according to claim 1 , comprising levetiracetam as active ingredient and
20.0 to 30.0% per weight of hydrophilic matrix agent,
0.5% per weight of gliding agent and
0.4 to 1.30% per weight of lubricant
with respect to the total weight of the core of the tablet.
21 . A pharmaceutical composition according to claim 1 , comprising levetiracetam as active ingredient and
5.0 to 59.0% per weight of hydroxypropylmethylcellulose,
0.3 to 2.5% per weight of anhydrous colloidal silica,
0.5 to 5.0% per weight of polyethylene glycol 6000, and
up to 1.0% per weight of magnesium stearate,
with respect to the total weight of the core of the tablet.
22 . A pharmaceutical composition according to claim 1 comprising levetiracetam as active ingredient and
8.0 to 50.0% per weight of hydroxypropylmethylcellulose,
0.3 to 2.5% per weight of anhydrous colloidal silica,
0.5 to 1.5% per weight of polyethylene glycol 6000, and
up to 0.5% per weight of magnesium stearate,
with respect to the total weight of the core of the tablet.
23 . A pharmaceutical composition according to claim 1 , comprising levetiracetam as active ingredient and
15.0 to 40.0% per weight of hydroxypropylmethylcellulose,
0.4 to 2.0% per weight of anhydrous colloidal silica,
0.7 to 1.5% per weight of polyethylene glycol 6000, and
0.1 to 0.3% per weight of magnesium stearate,
with respect to the total weight of the core of the tablet.
24 . A pharmaceutical composition according to claim 1 , comprising levetiracetam as active ingredient and
20.0 to 30.0% per weight of hydroxypropylmethylcellulose,
0 to 25% per weight of inert or lipophilic matrix agent,
0.5% per weight of anhydrous colloidal silica,
1.0% per weight of polyethylene glycol 6000, and
0.25% per weight of magnesium stearate,
with respect to the total weight of the core of the tablet.
25 . A pharmaceutical composition according to claim 1 , comprising levetiracetam as active ingredient and
20.0 to 30.0% per weight of hydroxypropylmethylcellulose,
0.5% per weight of anhydrous colloidal silica,
1.0% per weight of polyethylene glycol 6000, and
0.25% per weight of magnesium stearate,
with respect to the total weight of the core of the tablet.
26 . A pharmaceutical formulation in tablet form comprising levetiracetam having the following dissolution profile in water according to the USP 24 (apparatus n o 2, 100 rpm, aqueous medium 900 mL):
Time (h)
% dissolution
0.5
19 ± 4
1
27 ± 7
2
42 ± 8
4
64 ± 10
8
85 ± 10
12
98 ± 9.
27 . The formulation of claim 26 having the dissolution profile:
Time (h)
% dissolution
0.5
21
1
33
2
50
4
72
8
94
12
100.
28 . The formulation according to claim 26 comprising as a percentage by weight of the table core about 70% levetiracetam, about 19-28% hydroxypropyl methylcellulose, and, optionally, about 2-14% Povidone.
29 . The formulation of claim 1 comprising 30.0 to 85.0% per weight of levetiracetam with respect to the total weight of the core of the tablet.
30 . The formulation of claim 29 wherein the hydrophilic matrix agent is hydroxypropyl methylcellulose and further optionally comprising about 2-14% Povidone.