Oral formulations and lipophilic salts of methylnaltrexone

Abstract

The present invention provides compositions comprising methylnaltrexone or a salt thereof, and compositions and formulations thereof, for oral administration.

1 - 25 . (canceled) 
     
     
         26 . A pharmaceutical composition for oral administration comprising a solid dosage of (i) methylnaltrexone, or a pharmaceutically acceptable salt thereof, (ii) an amphiphilic pharmaceutically acceptable excipient, (iii) a chelating agent, and (iv) a disintegrant. 
     
     
         27 . The pharmaceutical composition of  claim 26 , wherein the methylnaltrexone, or a pharmaceutically acceptable salt thereof, is (R)—N-methylnaltrexone bromide. 
     
     
         28 . The pharmaceutical composition of  claim 27 , wherein the (R)—N-methylnaltrexone bromide is present at about 150 mg. 
     
     
         29 . The pharmaceutical composition of  claim 26 , wherein the chelating agent is EDTA or a salt thereof. 
     
     
         30 . The pharmaceutical composition of  claim 29 , wherein the chelating agent comprises edetate calcium disodium. 
     
     
         31 . The pharmaceutical composition of  claim 26 , wherein the disintegrant comprises a rapid acting disintegrant. 
     
     
         32 . The pharmaceutical composition of  claim 31 , wherein the disintegrant comprises an effervescent disintegrant. 
     
     
         33 . The pharmaceutical composition of  claim 26 , wherein the disintegrant comprises a combination of crospovidone and cross-linked sodium carboxymethyl cellulose. 
     
     
         34 . The pharmaceutical composition of  claim 26 , wherein the composition is a tablet. 
     
     
         35 . The pharmaceutical composition of  claim 34 , wherein the tablet is not enterically coated. 
     
     
         36 . The pharmaceutical composition of  claim 27 , wherein (R)—N-methylnaltrexone bromide is the sole active agent. 
     
     
         37 . The pharmaceutical composition of  claim 27 , wherein the amphiphilic pharmaceutically acceptable excipient is sodium dodecyl sulfate. 
     
     
         38 . The pharmaceutical composition of  claim 37 , wherein the ratio of (R)—N-methylnaltrexone bromide to sodium dodecyl sulphate is about 3:1 by weight. 
     
     
         39 . The pharmaceutical composition of  claim 26 , further comprising a binder. 
     
     
         40 . The pharmaceutical composition of  claim 39 , wherein the binder comprises microcrystalline cellulose. 
     
     
         41 . The pharmaceutical composition of  claim 26 , further comprising a glidant. 
     
     
         42 . The pharmaceutical composition of  claim 41 , wherein the glidant comprises colloidal silicon dioxide. 
     
     
         43 . A method for treating opioid induced constipation in a subject in need thereof, comprising administering the pharmaceutical composition of  claim 26  to the subject, thereby treating opioid induced constipation.