Compositions and methods of treating middle-of-the night insomnia

Abstract

The present invention provides compositions and methods for treating middle-of-the-night insomnia without residual sedative effects upon awakening by administering low doses (about 5 mg or less) of zolpidem or a salt thereof.

1 . A solid unit dosage composition for the treatment of MOTN insomnia, said composition comprising an effective amount of zolpidem or a salt thereof, formulated for delivery of zolpidem across a subject's oral mucosa, wherein said effective amount is an amount of less than 1.30×10 −5  moles of zolpidem, and is an amount sufficient to produce a plasma concentration between about 25 ng/ml and about 50 ng/ml within 20 minutes of administration, when evaluated in an appropriate patient population.  
   
   
       2 . A solid unit dosage composition of  claim 1 , which further provides 50% of the maximum plasma concentration (Cmax) of zolpidem in 10 minutes or less.  
   
   
       3 . A solid unit dosage composition of  claim 2 , which further provides blood levels of zolpidem that are less than 20 ng/ml at a time 4 hours after dosing.  
   
   
       4 . A solid unit dosage composition of  claim 1 , further comprising at least one pH-adjusting agent selected from the group consisting of a carbonate salt and a bicarbonate salt.  
   
   
       5 . A solid unit dosage composition of  claim 1 , further comprising a binary buffer system that raises the pH of said subject's saliva to a pH greater than about 8.5, irrespective of the starting pH of saliva.  
   
   
       6 . A solid unit dosage composition of  claim 5 , wherein the binary buffer system consists of sodium carbonate and sodium bicarbonate.  
   
   
       7 . A solid unit dosage composition of  claim 6 , in the form of a quick-dissolving tablet or lozenge.  
   
   
       8 . A solid unit dosage composition of  claim 5 , containing from 0.5 to 4.75 mg of zolpidem hemitartrate.  
   
   
       9 . A solid unit dosage composition of  claim 5 , containing from 1.5 to 2.5 mg of zolpidem hemitartrate.  
   
   
       10 . A solid unit dosage composition of  claim 5 , containing from 3.0 to 3.75 mg of zolpidem hemitartrate.  
   
   
       11 . A solid unit dosage composition of  claim 1 , wherein the zolpidem is delivered across at least one of the sublingual or buccal mucosa.  
   
   
       12 . A solid unit dosage composition for the treatment of MOTN insomnia, said composition comprising an amount of zolpidem or a salt thereof effective to produce sleep within 30 minutes of dosing a subject, but does not produce residual sedative effects when said subject is awakened at a time 4 hours after dosing, when the composition is evaluated in an appropriate patient population.  
   
   
       13 . A solid unit dosage composition of  claim 12 , further comprising at least one pH-adjusting agent.  
   
   
       14 . A solid unit dosage composition of  claim 12 , further comprising a binary buffer system.  
   
   
       15 . A solid unit dosage composition of  claim 14 , wherein said binary buffer system consists of a carbonate salt and a bicarbonate salt.  
   
   
       16 . A solid unit dosage composition of  claim 14 , in a dosage form for delivery of zolpidem across the subject's oral mucosa, wherein said binary buffer system raises the pH of said subject's saliva to a pH greater than about 8.5, irrespective of the starting pH of saliva.  
   
   
       17 . A solid unit dosage composition of  claim 16 , containing less than 5 mg of zolpidem hemitartrate.  
   
   
       18 . A solid unit dosage composition of  claim 17 , containing from 1.5 to 2.5 mg of zolpidem hemitartrate.  
   
   
       19 . A solid unit dosage composition of  claim 17 , containing from 3.0 to 3.75 mg of zolpidem hemitartrate.  
   
   
       20 . A solid unit dosage composition of  claim 16 , in the form of a quick-dissolving lozenge or tablet.  
   
   
       21 - 185 . (canceled)