| 摘要 |
A sustained-release pharmaceutical composition in a form of an orally deliverable tablet comprises as active pharmaceutical agent a compound of formula or a pharmaceutically acceptable salt thereof, wherein R<1>, R<2 >and R<3 >are the same or different and are H, C1-6 alkyl (optionally phenyl substituted), C3-5 alkenyl or alkynyl or C3-10 cycloalkyl, or where R<3 >is as above and R<1 >and R<2 >are cyclized with the attached N atom to form pyrrolidinyl, piperidinyl, morpholinyl, 4-methylpiperazinyl or imidazolyl groups; X is H, F, Cl, Br, I, OH, C1-6 alkyl or alkoxy, CN, carboxamide, carboxyl or (C1-6 alkyl)carbonyl; A is CH, CH2, CHF, CHCl, CHBr, CHI, CHCH3, C=O, C=S, CSCH3, C=NH, CNH2, CNHCH3, CNHCOOCH3, CNHCN, SO2 or N; B is CH, CH2, CHF, CHCl, CHBr, CHI, C=O, N, NH or NCH3, and n is 0 or 1; and D is CH, CH2, CHF, CHCl, CHBr, CHI, C=O, O, N, NH or NCH3. The agent is dispersed in a matrix comprising a hydrophilic polymer and a starch having a tensile strength of at least about 0.15 kN cm<-2 >at a solid fraction representative of the tablet. The composition exhibits sustained-release properties effective for treatment of Parkinson's disease. The tablet is optionally coated. Tablets of the invention have improved resistance to attrition or erosion during manufacture, packaging and handling.
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