Pharmaceutical Compositions Comprising 2-Oxo-1-Pyrrolidine Derivatives
The present invention relates to an immediate release formulation of pharmaceutical compounds.
1 . An oral pharmaceutical composition in a solid form comprising an active ingredient, a cyclodextrin excipient, and, optionally, an additional excipient or excipients, a disintegrant, a lubricant, and/or a diluent, wherein the weight of cyclodextrin is 0.1% to 60% of the total weight of the composition; and wherein the active ingredient is an 2-oxo-1-pyrrolidine derivative of formula (I),
wherein,
R 1 is C 1-10 alkyl or C 2-6 alkenyl;
R 2 is C 1-10 alkyl or C 2-6 alkenyl;
X is —CONR 4 R 5 , —COOH, —COOR 3 or —CN;
R 3 is C 1-10 alkyl;
R 4 is hydrogen or C 1-10 alkyl; and
R 5 is hydrogen or C 1-10 alkyl.
2 . The composition according to claim 1 , wherein R 1 is hydrogen, n-propyl or 2,2-difluororovinyl; R 2 is ethyl; and X is —CONH 2 .
3 . The composition according to claim 1 , wherein the cyclodextrin is chosen among alpha cyclodextrin, beta cyclodextrin, hydroxypropyl beta cyclodextrin, methyl beta cyclodextrin, sulfobutyl beta cyclodextrin, gamma cyclodextrin, and hydroxypropyl gamma cyclodextrin.
4 . The composition according to claim 3 , wherein the cyclodextrin is a beta cyclodextrin.
5 . The composition according to claim 1 , wherein the cyclodextrin is a beta cyclodextrin having a water content between 5 and 16% (w/w).
6 . The composition according to claim 1 , wherein the composition is a homogeneous blend.
7 . The composition according to claim 1 , wherein the weight of the cyclodextrin is 1.0 to 15.0% of the weight of the composition.
8 . The composition according to claim 1 , wherein the composition also comprises a disintegrant.
9 . The composition according to claim 8 , wherein the disintegrant is sodium croscarmellose.
10 . The composition according to claim 8 , wherein the weight of the disintegrant is 1.5 to 8% of the weight of the composition.
11 . The composition according to claim 1 , wherein the composition comprises a diluent.
12 . The composition according to claim 11 , wherein the diluent is a mixture of lactose monohydrate and anhydrous lactose.
13 . The composition according to claim 11 , wherein the weight of the diluent is 30 to 90% of the weight of the composition.
14 . The composition according to claim 1 , wherein the composition also comprises a lubricant.
15 . The composition according to claim 14 , wherein the lubricant is magnesium stearate.
16 . The composition according to claim 14 , wherein the weight of the lubricant is 0.01 to 2.0% of the total weight of the composition.
17 . The composition according to claim 1 , wherein the composition comprises
brivaracetam as active ingredient;
0.1 to 60% by weight of at least a cyclodextrin agent;
0.5 to 25% by weight of disintegrant; and
5 to 95% by weight of diluent;
all weights with respect to the total weight of the composition.
18 . A process for preparing a composition according to claim 1 , wherein the process comprises a direct compression of the composition.
19 . The process according to claim 18 , wherein the process comprises
mixing the active ingredient, the cyclodextrin excipient, and any other excipients, disintegrates, lubricants, and diluents; and
compressing the mixture in order to obtain a tablet.