| 摘要 |
Pharmaceutical compositions of metabotropic glutamate 5 receptor (mGlu5) antagonists or a pharmacologically acceptable salt thereof are disclosed. The compositions contain the therapeutic active compound with non-ionic polymer and ionic polymer, binder and fillers in either matrix pellet, matrix tablet or coated pellets. The compositions provide a pH-independent in vitro release profile with NMT 70% in one hour, NMT 85% in 4 hour, and NLT 80% in 8 hours. The compositions are useful for the treatment of CNS disorders, such as Treatment-Resistant Depression (TRD) and Fragile X Syndrome. |
| 主权项 |
1. A pharmaceutical composition comprising a compound of formula Iformula Iwherein
one of A or E is N and the other is C; R1 is halogen or cyano; R2 is lower alkyl; R3 is aryl or heteroaryl, each of which is optionally substituted by one, two or three substituents chosen from halogen, lower alkyl, lower alkoxy, cycloalkyl, lower haloalkyl, lower haloalkoxy, cyano, or NR′R″,
or by1-morpholinyl,1-pyrrolidinyl, optionally substituted by (CH2)mOR,piperidinyl, optionally substituted by (CH2)mOR,1,1-dioxo-thiomorpholinyl,piperazinyl, optionally substituted by lower alkyl or (CH2)m-cycloalkyl; R is hydrogen, lower alkyl or (CH2)m-cycloalkyl; R′ and R″ are each independently hydrogen, lower alkyl, (CH2)m-cycloalkyl or (CH2)nOR; m is 0 or 1; n is 1 or 2; and R4 is CHF2, CF3, C(O)H, or CH2R5, wherein R5 is hydrogen, OH, C1-C6-alkyl or C3-C12-cycloalkyl; and pharmaceutically acceptable salts thereof, a rate-controlling polymer, and a pH responding polymer. |
