Opioid formulations

Abstract

The present invention provides high-concentration formulations of opioids such as fentanyl or fentanyl congeners. The formulation of the invention comprises fentanyl or a fentanyl congener in concentrations significantly in excess of conventional formulations, e.g., on the order about 2-fold to about 10,000-fold greater than conventional formulations, e.g., currently commercially available formulations. These formulations are particularly useful for long-term delivery to a subject suffering from pain. The invention further provides drug delivery devices comprising the high-concentration opioid formulations, and further provides methods of alleviating pain in a subject, comprising administering the high-concentration formulations to a subject in need thereof.

1 . A pharmaceutical formulation comprising fentanyl or a fentanyl congener and a non-aqueous carrier, wherein the fentanyl or fentanyl congener is present in the formulation at a concentration of at least about 500 μg/mL. 
     
     
         2 . The pharmaceutical formulation according to  claim 1 , wherein the non-aqueous carrier is a lower molecular weight alcohol comprising an aromatic moiety. 
     
     
         3 . The pharmaceutical formulation according to  claim 2 , wherein the alcohol is benzyl alcohol. 
     
     
         4 . The pharmaceutical formulation according to  claim 1 , wherein the non-aqueous carrier comprises a non-ionic surfactant and an alcohol ester. 
     
     
         5 . The pharmaceutical formulation according to  claim 4 , wherein the non-ionic surfactant is selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 80, and sorbitan trioleate. 
     
     
         6 . The pharmaceutical formulation according to  claim 4 , wherein the alcohol is benzyl alcohol. 
     
     
         7 . A pharmaceutical formulation comprising fentanyl or a fentanyl congener in a concentration of from about 0.5 mg/mL to about 500 mg/mL in a lower molecular weight alcohol which comprises an aromatic moiety. 
     
     
         8 . The pharmaceutical formulation of  claim 7 , comprising fentanyl or fentanyl congener in a concentration of from about 50 mg/mL to about 400 mg/mL. 
     
     
         9 . The pharmaceutical formulation of  claim 7 , wherein the fentanyl congener is sufentanil. 
     
     
         10 . The pharmaceutical formulation of  claim 7 , wherein the lower molecular weight alcohol is benzyl alcohol. 
     
     
         11 . The pharmaceutical formulation of  claim 7 , wherein the fentanyl or a fentanyl congener is present in the formulation as a fentanyl base or a fentanyl congener base. 
     
     
         12 . A pharmaceutical formulation comprising fentanyl or a fentanyl congener in a concentration from about 0.5 mg/mL to about 500 mg/mL, and a nonionic surfactant in a concentration of from about 50 mg/mL to about 200 mg/mL, in an alcohol ester which comprises an aromatic moiety. 
     
     
         13 . The pharmaceutical formulation of  claim 12 , comprising fentanyl or fentanyl congener in a concentration of from about 50 mg/mL to about 250 mg/mL. 
     
     
         14 . The pharmaceutical formulation of  claim 12 , wherein the fentanyl congener is sufentanil. 
     
     
         15 . The pharmaceutical formulation of  claim 12 , wherein the nonionic surfactant is selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 80, and sorbitan trioleate. 
     
     
         16 . The pharmaceutical formulation of  claim 12 , wherein the alcohol ester is benzyl benzoate. 
     
     
         17 . The pharmaceutical formulation of  claim 12 , wherein the fentanyl or fentanyl congener is present in the formulation as a fentanyl base or a fentanyl congener base. 
     
     
         18 . A dosage form comprising a formulation according to  claim 1 . 
     
     
         19 . A method of treating pain in a subject suffering from pain, comprising administering to a subject suffering from pain a formulation according to  claim 1  in an amount effective to alleviate pain in the subject. 
     
     
         20 .- 26 . (canceled)