Gabapentin-containing Solid Compositions and Process for Preparing the Same

A process for the preparation of a solid composition containing a 4-amino-3-substituted-butanoic acid derivative having the general formula

• wherein,
• R1 is a hydrogen atom, a hydroxyl group, a methyl group or an ethyl group;
• R2 is a monovalent group selected from:
• a straight or branched alkyl group of 3-8 carbon atoms;
• a straight or branched alkylene group of 3-8 carbon atoms;
• a straight or branched alkyl group of 3-8 carbon atoms which is mono- or di-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkoxy group, an alkylthio group, an amino group, a nitro group, an oxo group, a carboxyl group or a carboalkoxy group;
• a cycloalkyl group of 3-8 carbon atoms;
• a cycloalkyl group of 3-8 carbon atoms which is mono-, di- or tri-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkyl group, an alkoxy group, an alkylthio group, an amino group, a nitro group, an oxo group, a carboxyl group or a carboalkoxy group;
• a condensed ring group formed by ortho-fusion of a phenyl ring with a cycloalkyl group of 4-8 carbon atoms;
• a condensed ring group formed by ortho-fusion of a phenyl ring with a cycloalkyl group of 4-8 carbon atoms wherein said phenyl ring is mono-, di- or tri-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkyl group, an alkoxy group, an alkylthio group, an amino group, a nitro group, a carboxyl group or a carboalkoxy group;
• a condensed ring group formed by ortho-fusion of a phenyl ring with a cycloalkenyl group of 5-8 carbon atoms or a cycloalkanedienyl group of 5-8 carbon atoms;
• a condensed ring group formed by ortho-fusion of a phenyl ring with a cycloalkenyl group of 5-8 carbon atoms or a cycloalkanedienyl group of 5-8 carbon atoms wherein said phenyl ring is mono-, di- or tri-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkyl group, an alkoxy group, an alkylthio group, an amino group, a nitro group, a carboxyl group or a carboalkoxy group;
• an alkylcycloalkyl group wherein said cycloalkyl has 3-8 carbon atoms and is linked to an alkylene group having 1-4 carbon atoms optionally interrupted with —O—, —S— or —SS—;
• an alkylcycloalkyl group wherein said cycloalkyl has 3-8 carbon atoms, is linked to an alkylene group having 1-4 carbon atoms optionally interrupted with —O—, —S— or —SS— and is mono-, di- or tri-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkyl group, an alkoxy group, an alkylthio group, an amino group, a nitro group, an oxo group, a carboxyl group or a carboalkoxy group;
• a cycloalkyl group of 5-8 carbon atoms wherein one of the methylene groups (—CH2—) is replaced by —O—, —NH—, —S—, —SO— or —S(O)2—;
• a cycloalkyl group of 5-8 carbon atoms wherein one of the methylene groups (—CH2—) is replaced by —O—, —NH—, —S—, —SO— or —S(O)2—, and one or two of the unsubstituted methylene groups (—CH2—) are mono- or di-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkyl group, an alkoxy group, an alkylthio group, an amino group, a nitro group, an oxo group, a carboxyl group or a carboalkoxy group;
• a cycloalkenyl group of 5-8 carbon atoms or a cycloalkanedienyl group of 5-8 carbon atoms, one of the methylene groups (—CH2—) in said cycloalkenyl ring or cycloalkanedienyl ring being replaced by —O—, —NH—, ═N—, —S—, —SO— or —S(O)2—;
• a cycloalkenyl group of 5-8 carbon atoms or a cycloalkanedienyl group of 5-8 carbon atoms, one of the methylene groups (—CH2—) in said cycloalkenyl ring or cycloalkanedienyl ring being replaced by —O—, —NH—, ═N—, —S—, —SO— or —S(O)2—, and one or two of the unsubstituted methylene groups (—CH2—) being mono- or di-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkyl group, an alkoxy group, an alkylthio group, an amino group, a nitro group, an oxo group, a carboxyl group or a carboalkoxy group;
• a condensed ring group formed by ortho-fusion of a phenyl ring with a cycloalkyl group of 5-8 carbon atoms wherein one of the methylene groups (—CH2—) is replaced by —O—, —NH—, —S—, —SO— or —S(O)2—;
• a condensed ring group formed by ortho-fusion of a phenyl ring with a cycloalkyl group of 5-8 carbon atoms wherein one of the methylene groups (—CH2—) is replaced by —O—, —NH—, —S—, —SO— or —S(O)2—, said phenyl group being mono- or di-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkyl group, an alkoxy group, an alkylthio group, an amino group, a nitro group, a carboxyl group or a carboalkoxy group;
• a condensed ring group formed by ortho-fusion of a phenyl ring with a cycloalkenyl group of 5-8 carbon atoms or a cycloalkanedienyl group of 5-8 carbon atoms, one of the methylene groups (—CH2—) in said cycloalkenyl ring or cycloalkanedienyl ring being replaced by —O—, —NH—, ═N—, —S—, —SO— or —S(O)2—;
• a condensed ring group formed by ortho-fusion of a phenyl ring with a cycloalkenyl group of 5-8 carbon atoms or a cycloalkanedienyl group of 5-8 carbon atoms, one of the methylene groups (—CH2—) in said cycloalkenyl ring or cycloalkanedienyl ring being replaced by —O—, —NH—, ═N—, —S—, —SO— or —S(O)2—, said phenyl ring being mono- or di-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkyl group, an alkoxy group, an alkylthio group, an amino group, a nitro group, a carboxyl group or a carboalkoxy group;
• an alkylcycloalkyl group wherein said cycloalkyl has 5-8 carbon atoms and is linked to an alkylene group having 1-4 carbon atoms optionally interrupted with —O—, —S— or —SS—, one of the methylene groups (—CH2—) in said cycloalkyl ring being replaced by —O—, —NH—, —S—, —SO— or —S(O)2—;
• an alkylcycloalkyl group wherein said cycloalkyl has 5-8 carbon atoms and is linked to an alkylene group having 1-4 carbon atoms optionally interrupted with —O—, —S— or —SS—, and one of the methylene groups (—CH2—) in said cycloalkyl ring being replaced by —O—, —NH—, —S—, —SO— or —S(O)2— and one or two of the unsubstituted methylene groups (—CH2—) being mono-, di- or tri-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkyl group, an alkoxy group, an alkylthio group, an amino group, a nitro group, an oxo group, a carboxyl group or a carboalkoxy group;
• a phenyl or naphthyl group;
• a phenyl group substituted with a methylenedioxy group;
• a phenyl or naphthyl group which is mono-, di- or tri-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkyl group, an alkoxy group, an amino group, a nitro group, a carboxyl group, a phenoxy group, a phenylmethoxy group, a phenylmethoxy group wherein said phenyl ring is mono-substituted with a halogen atom, trifluoromethyl group, an alkoxy group, an amino group, a nitro group, a carboxyl group or a carboalkoxy group, a cycloalkylmethoxy group having 5-8 carbon atoms in the cycloalkyl ring, a cycloalkenylmethoxy group having 5-8 carbon atoms in the cycloalkenyl ring, a cycloalkanedienylmethoxy group having 5-8 carbon atoms in the cycloalkanedienyl ring, a cycloalkylmethoxy group wherein one of the methylene groups (—CH2—) in said cycloalkyl ring having 5-8 carbon atoms is replaced by —O—, —NH—, —S—, —SO— or —S(O)2—, a cycloalkenylmethoxy group wherein one of the methylene groups (—CH2—) in said cycloalkenyl ring having 5-8 carbon atoms is replaced by —O—, —NH—, ═N—, —S—, —SO— or —S(O)2—, a cycloalkanedienyl-methoxy group wherein one of the methylene groups (—CH2—) in said cycloalkanedienyl ring having 5-8 carbon atoms is replaced by —O—, —NH—, ═N—, —S—, —SO— or —S(O)2— group, a cycloalkylmethoxy group having 5-8 carbon atoms in the cycloalkyl ring wherein said cycloalkyl ring is mono-substituted with a halogen atom, trifluoromethyl group, a hydroxy group, an alkyl group, an alkoxy group, an amino group, a nitro group, a carboxyl group or a carboalkoxy group and one of the methylene groups (—CH2—) in said cycloalkyl ring is replaced by —O—, —NH—, —S—, —SO— or —S(O)2—, a cycloalkenylmethoxy group having 5-8 carbon atoms in the cycloalkenyl ring wherein said cycloalkenyl ring is mono-substituted with a halogen atom, a trifluoromethyl group, a hydroxy group, an alkyl group, an alkoxy group, an amino group, a nitro group, an oxo group, a carboxyl group or a carboalkoxy group and one of the methylene groups (—CH2—) in said cycloalkenyl ring is replaced by —O—, —NH—, ═N—, —S—, —SO— or —S(O)2—, or a cycloalkanedienylmethoxy group having 5-8 carbon atoms in the cycloalkanedienyl ring wherein said cycloalkanedienyl ring is mono-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkyl group, an alkoxy group, an amino group, a nitro group, an oxo group, a carboxyl group or a carboalkoxy group and one of the methylene groups (—CH2—) in said cycloalkanedienyl ring is replaced by —O—, —NH—, ═N—, —S—, —SO— or —S(O)2—;
• an alkylphenyl group wherein said phenyl group is linked to an alkylene group having 1-4 carbon atoms optionally interrupted with —O—, —S— or —SS—;
• an alkyl-O—, —S— or —SS-phenyl group wherein said phenyl group is linked to an alkylene group having 1-4 carbon atoms via —O—, —S— or —SS—;
• an —O—, —S— or —SS-phenyl group;
• a diphenylamino group;
• an alkylphenyl group wherein said phenyl group is linked to an alkylene group having 1-4 carbon atoms optionally interrupted with —O—, —S— or —SS— and mono-, di- or tri-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, a alkyl group, an alkoxy group, an amino group, a nitro group or a carboxyl group;
• an alkyl-O—, —S— or —SS-phenyl group wherein said phenyl group is linked to an alkylene group having 1-4 carbon atoms via —O—, —S— or —SS— and mono-, di- or tri-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkyl group, an alkoxy group, an amino group, a nitro group or a carboxyl group;
• an —O—, —S— or —SS-phenyl group wherein said phenyl group is mono-, di- or tri-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkyl group, an alkoxy group, an amino group, a nitro group or a carboxyl group;
• or
• R1 and R2, together with the carbon atom to which they are attached, may form a divalent group selected from:
• a cycloalkylidene group of 5-8 carbon atoms;
• a cycloalkylidene group of 5-8 carbon atoms which is mono-, di-, tri- or tetra-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkyl group, an alkoxy group, an alkylthio group, a cycloalkyl group, a phenyl group, an amino group, a nitro group or a carboxyl group;
• a cycloalkylidene group of 5-8 carbon atoms wherein one of the methylene groups (—CH2—) in said cycloalkyl ring is replaced by —O—, —NH—, —S—, —SO— or —S(O)2—;
• a cycloalkylidene group of 5-8 carbon atoms wherein one of the methylene groups (—CH2—) in said cycloalkyl ring is replaced by —O—, —NH—, —S—, —SO— or —S(O)2-group and one or more of the unsubstituted methylene groups (—CH2—) in said cycloalkyl ring are mono-, di-, tri- or tetra-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkyl group, an alkoxy group, an alkylthio group, an amino group, a nitro group, an oxo group, a carboxyl group or a carboalkoxy group;
• a cycloalkenylidene group of 5-8 carbon atoms or a cycloalkanedienylidene group of 5-8 carbon atoms;
• a cycloalkenylidene group of 5-8 carbon atoms or a cycloalkanedienylidene group of 5-8 carbon atoms which is mono-, di-, tri- or tetra-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkyl group, an alkoxy group, an alkylthio group, a cycloalkyl group, a phenyl group, an amino group, a nitro group, an oxo group, a carboxyl group or a carboalkoxy group;
• a cycloalkenylidene group of 5-8 carbon atoms or a cycloalkanedienylidene group of 5-8 carbon atoms wherein one of the methylene groups (—CH2—) in said cycloalkenyl ring or cycloalkanedienyl ring is replaced by —O—, —NH—, ═N—, —S—, —SO— or —S(O)2—;
• a cycloalkenylidene group of 5-8 carbon atoms or a cycloalkanedienylidene group of 5-8 carbon atoms wherein one of the methylene groups (—CH2—) in said cycloalkenyl ring or cycloalkanedienyl ring is replaced by —O—, —NH—, ═N—, —S—, —SO— or —S(O)2— group and one or more of the unsubstituted methylene groups (—CH2—) in said cycloalkenyl ring or cycloalkanedienyl ring are mono-, di-, tri- or tetra-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkyl group, an alkoxy group, an alkylthio group, an amino group, a nitro group, an oxo group, a carboxyl group or a carboalkoxy group;
• a condensed ring group formed by ortho-fusion of a phenyl ring with a cycloalkylidene group of 4-8 carbon atoms;
• a condensed ring group formed by ortho-fusion of a phenyl ring with a cycloalkylidene group of 4-8 carbon atoms, said phenyl ring being mono-, di-, tri- or tetra-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkyl group, an alkoxy group, an alkylthio group, an amino group, a nitro group, a carboxyl group or a carboalkoxy group;
• a condensed ring group formed by ortho-fusion of a phenyl ring with a cycloalkenylidene group of 5-8 carbon atoms or a cycloalkanedienylidene group of 5-8 carbon atoms;
• a condensed ring group formed by ortho-fusion of a phenyl ring with a cycloalkenylidene group of 5-8 carbon atoms or a cycloalkanedienylidene group of 5-8 carbon atoms, said phenyl ring being mono- or di-substituted with a halogen atom, a trifluoromethyl group, a hydroxyl group, an alkyl group, an alkoxy group, an alkylthio group, an amino group, a nitro group, a carboxyl group or a carboalkoxy group, which comprises combining the 4-amino-3-substituted-butanoic acid derivative with a humectant and, if necessary, an auxiliary agent for manufacturing a pharmaceutical preparation.