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 claims  1 ,  7  or  12 .  
   
   
       19 . A method of treating pain in a subject suffering from pain, comprising administering to a subject suffering from pain a formulation according to claims  1 ,  7  or  12  in an amount effective to alleviate pain in the subject.  
   
   
       20 . A pharmaceutical formulation comprising sufentanil and a non-aqueous diluent, wherein sulfentanil is present in the formulation in a concentration greater than about 500 μg/mL.  
   
   
       21 . The pharmaceutical formulation of  claim 20 , wherein the formulation comprises a lower molecular weight alcohol comprising an aromatic moiety.  
   
   
       22 . The pharmaceutical formulation of  claim 21 , wherein the lower molecular weight alcohol is benzyl alcohol.  
   
   
       23 . The pharmaceutical formulation of  claim 20 , wherein the formulation comprises a nonionic surfactant in a concentration of from about 50 mg/mL to about 200 mg/mL, and an alcohol ester which comprises an aromatic moiety.  
   
   
       24 . The pharmaceutical formulation of  claim 23 , wherein the alcohol ester is benzyl benzoate and wherein the nonionic surfactant is selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 80, and sorbitan trioleate.  
   
   
       25 . A drug dosage form comprising a formulation according  claim 20 .  
   
   
       26 . A method of treating pain in a subject suffering from pain, comprising administering to a subject suffering from pain a formulation according to  claim 20 , thereby alleviating pain in the subject.