Pharmaceutical formulations useful in the treatment of insomnia

Abstract

There is provided a formulation suitable for transmucosal administration comprising a short acting hypnotic drug, which formulation provides a measurable plasma concentration of drug within 10 minutes of administration. The formulation is capable of providing sleep on demand, and preferably comprises particles of drug, for example zolpidem or a pharmaceutically-acceptable salt thereof and a mucoadhesion promoting agent, such as sodium carboxymethylcellulose, which particles of drug and mucoadhesive are presented upon the surface of larger carrier particles.

1 . A pharmaceutical formulation suitable for transmucosal administration comprising a short acting hypnotic drug, which formulation provides a measurable plasma concentration of drug within 10 minutes of administration. 
     
     
         2 . A formulation as claimed in  claim 1 , wherein, when measured in a standard in vitro paddle apparatus according to the United States Pharmacopoeia, using a phosphate buffer at pH 6.8 (USP) as dissolution medium, at least 50% of the drug that is initially present in the formulation is released within 5 minutes. 
     
     
         3 . A formulation as claimed in  claim 2 , wherein the drug is released within 3 minutes. 
     
     
         4 . A transmucosal formulation comprising a short acting hypnotic drug. 
     
     
         5 . A formulation as claimed in  claim 4 , which is suitable for providing sleep on demand. 
     
     
         6 . A formulation as claimed in  claim 1 , wherein the formulation provides for a time difference between:
 (a) the first measurable; and   (b) the maximum measured   plasma concentration of drug following administration of the formulation, which time difference is within the range of about 80 minutes to about 160 minutes.   
     
     
         7 . A formulation as claimed in  claim 1 , wherein the formulation provides for a plasma concentration of drug that is capable of maintaining sleep at least about 6 hours after administration. 
     
     
         8 . A formulation as claimed in  claim 1 , wherein the formulation provides for a plasma concentration of drug that does not result in decreased alertness and/or impairment of psychomotor function in a patient following sleep at least about 7 hours after administration. 
     
     
         9 . A formulation as claimed in  claim 1 , which is suitable for administration across the oral mucosa. 
     
     
         10 . A formulation as claimed in  claim 9 , which is a sublingual tablet. 
     
     
         11 . A formulation as claimed in  claim 10 , which comprises particles of:
 (a) the short acting hypnotic drug; and   (b) a mucoadhesion promoting agent,   which particles of components (a) and (b) are each presented, at least in part, upon the surfaces of larger carrier particles.   
     
     
         12 . A formulation as claimed in  claim 1 , wherein the drug is zolpidem or a pharmaceutically acceptable salt thereof. 
     
     
         13 . A formulation as claimed in  claim 12  wherein the salt is zolpidem hemitartrate. 
     
     
         14 . A formulation as claimed in  claim 1 , wherein the drug is in the form of microparticles.