Formulations comprising 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol

Abstract

A solid pharmaceutical composition suitable for oral administration, comprising: (a) a S1P receptor modulator; (b) a filler, and (c) a cyclodextrin.

1 . A solid pharmaceutical composition suitable for oral administration, comprising
 a) a first compound selected from 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol, a pharmaceutically acceptable salt thereof, and a phosphate derivative thereof,   b) a filler, and   c) a stabilizer comprising a cyclodextrin or a derivative thereof,   wherein the cyclodextrin or derivative thereof is natural cyclodextrin, a branched cyclodextrin, an alkyl-cyclodextrin or a hydroxyalkyl-cyclodextrin, and wherein the pharmaceutical composition is in unit dosage form, each unit comprising about 0.5 mg of the first compound.   
     
     
         2 . The composition according to  claim 1 , wherein the filler comprises a sugar alcohol. 
     
     
         3 . The composition according to  claim 1 , further comprising a binder. 
     
     
         4 . The composition according to  claim 1 , further comprising a lubricant. 
     
     
         5 . The composition according to  claim 1 , wherein the stabilizer comprises hydroxypropyl-beta-cyclodextrin. 
     
     
         6 . The composition according to  claim 1 , wherein the first compound is 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol or a pharmaceutically acceptable salt thereof. 
     
     
         7 . A method of treating multiple sclerosis in a patient in need thereof, comprising administering a therapeutically effective amount of the solid pharmaceutical composition according to  claim 1 . 
     
     
         8 . The composition according to  claim 2 , wherein the sugar alcohol is mannitol. 
     
     
         9 . The composition according to  claim 3 , wherein the binder is hydroxypropyl cellulose. 
     
     
         10 . The A composition according to  claim 1 , wherein the cyclodextrin or derivative thereof is selected from the group consisting of α-cyclodextrin; β-cyclodextrin, γ-cyclodextrin; hydroxypropyl-cyclodextrin, sulfobutylether β-cyclodextrin, dodecakis-2,6,O-methyl-α-cyclodextrin, tetradecakis-2,6,O-methyl-β-cyclodextrin, hexadecakis-2,6,O-methyl-γ-cyclodextrin, tetradecakis-2,6,O-ethyl-β-cyclodextrin, α-cyclodextrin partially etherized with 2-hydroxypropyl, β-cyclodextrin partially etherized with 2-hydroxypropyl, branched α-cyclodextrin, and branched β-cyclodextrin where glucose or maltose has been bound via α-1,6 glucoside bound. 
     
     
         11 . The composition according to  claim 4 , wherein the lubricant is magnesium stearate.