Transoral dosage forms comprising sufentanil and naloxone

Abstract

The invention pertains to methods that include administering to a subject a transoral dosage form comprising a pharmaceutical carrier and sufentanil, and maintaining a mean pH ranging from about 3.5 to about 5.5 during a dosing period after administration of the transoral dosage form as determined using an in vitro donor media test. Related dosage forms are also disclosed. Also disclosed are transoral dosage forms and related methods, wherein a transoral dosage form may comprise: (1) about 5 to about 1000 micrograms of sufentanil; (2) about 50 micrograms to about 100 milligrams of naloxone; and (3) acidifying material in an amount sufficient to provide a mean pH ranging from about 3.5 to about 5.5 during a dosing period after administration of the transoral dosage form as determined using an in vitro donor media test; wherein the dosing period begins no earlier than about 1 minute after administration of the transoral dosage form, and ends no later than about 120 minutes after administration of the transoral dosage form.

1 . A method comprising:
 administering to a subject a transoral dosage form comprising a pharmaceutical carrier and sufentanil, and   maintaining a mean pH ranging from about 3.5 to about 5.5 during a dosing period after administration of the transoral dosage form as determined using an in vitro donor media test;   wherein the dosing period begins no earlier than about 1 minute after administration of the transoral dosage form, and ends no later than about 120 minutes after administration of the transoral dosage form.   
     
     
         2 . The method of  claim 1 , wherein the dosing period begins no earlier than about 2 minutes after administration of the transoral dosage form, and ends no later than about 60 minutes after administration of the transoral dosage form. 
     
     
         3 . The method of  claim 2 , wherein the dosing period begins no earlier than about 2 minutes after administration of the transoral dosage form, and ends no later than about 30 minutes after administration of the transoral dosage form. 
     
     
         4 . The method of  claim 1 , wherein the dosing period begins no earlier than about 3 minutes after administration of the transoral dosage form, and ends no later than about 60 minutes after administration of the transoral dosage form. 
     
     
         5 . The method of  claim 4 , wherein the dosing period begins no earlier than about 4 minutes after administration of the transoral dosage form, and ends no later than about 60 minutes after administration of the transoral dosage form. 
     
     
         6 . The method of  claim 5 , wherein the dosing period begins no earlier than about 5 minutes after administration of the transoral dosage form, and ends no later than about 60 minutes after administration of the transoral dosage form. 
     
     
         7 . The method of  claim 1 , wherein the transoral dosage form comprises a transoral dosage form having a fixed drug releasing area. 
     
     
         8 . The method of  claim 1 , wherein the transoral dosage form comprises a transoral dosage form having a variable drug releasing area. 
     
     
         9 . The method of  claim 1 , wherein the transoral dosage form comprises a gel dosage form. 
     
     
         10 . The method of  claim 1 , wherein the sufentanil comprises a pharmaceutically acceptable salt of sufentanil free base. 
     
     
         11 . The method of  claim 10 , wherein the pharmaceutically acceptable salt comprises sufentanil citrate. 
     
     
         12 . The method of  claim 1 , wherein the mean pH is maintained in a range from about 4.5 to about 5.5. 
     
     
         13 .- 15 . (canceled) 
     
     
         16 . A transoral dosage form comprising:
 about 5 to about 1000 micrograms of sufentanil; and   acidifying material in an amount sufficient to provide a mean pH ranging from about 3.5 to about 5.5 during a dosing period after administration of the transoral dosage form as determined using an in vitro donor media test;   wherein the dosing period begins no earlier than about 1 minute after administration of the transoral dosage form, and ends no later than about 120 minutes after administration of the transoral dosage form.   
     
     
         17 . The transoral dosage form of  claim 16 , comprising sufentanil citrate. 
     
     
         18 . The transoral dosage form of  claim 16 , wherein the acidifying material comprises an acid or a buffer. 
     
     
         19 .- 32 . (canceled) 
     
     
         33 . A method comprising:
 administering to a subject a transoral dosage form comprising
 (1) sufentanil; 
 (2) naloxone; and 
 (3) a pharmaceutical carrier, and 
   maintaining a mean pH ranging from about 3.5 to about 5.5 during a dosing period after administration of the transoral dosage form as determined using an in vitro donor media test;   wherein the dosing period begins no earlier than about 1 minute after administration of the transoral dosage form, and ends no later than about 120 minutes after administration of the transoral dosage form.   
     
     
         34 . The method of  claim 33 , wherein the dosing period begins no earlier than about 2 minutes after administration of the transoral dosage form, and ends no later than about 60 minutes after administration of the transoral dosage form. 
     
     
         35 . The method of  claim 34 , wherein the dosing period begins no earlier than about 2 minutes after administration of the transoral dosage form, and ends no later than about 30 minutes after administration of the transoral dosage form. 
     
     
         36 . The method of  claim 33 , wherein the dosing period begins no earlier than about 3 minutes after administration of the transoral dosage form, and ends no later than about 60 minutes after administration of the transoral dosage form. 
     
     
         37 . The method of  claim 36 , wherein the dosing period begins no earlier than about 4 minutes after the in vitro administration of the transoral dosage form, and ends no later than about 60 minutes after the in vitro administration of the transoral dosage form. 
     
     
         38 .- 68 . (canceled)