Synergistic mixed poloxamer systmes for the solubilisation of drugs

Abstract

Drugs which are difficult to solubilise in water, and especially those which otherwise cause pain on injection, can be readily formulated and typically administered with substantially less pain when solubilised in synergistic, aqueous micellar preparations of poloxamers. Such preparations may also be prepared with less, or without, co-solvents.

1 . An aqueous preparation comprising: 
 a drug, other than propofol, that is poorly soluble in water, and    a synergistic mixture of poloxamers which, together with water, solubilize more of said drug than an equivalent amount of any individual poloxamer of the mixture under the same conditions.    
     
     
         2 . A preparation according to  claim 1 , wherein water forms at least 85% w/v of that portion of the preparation not made up by poloxamers and drug.  
     
     
         3 . A preparation according to  claim 1 , wherein each poloxamer comprises at least 10% w/w of total poloxamer.  
     
     
         4 . A preparation according to  claim 3 , wherein each poloxamer comprises at least 20% w/w of total poloxamer.  
     
     
         5 . A preparation according to  claim 1 , wherein the mixture comprises only two poloxamers.  
     
     
         6 . A preparation according to  claim 5  wherein the ratio of one poloxamer to the other is between 7:3 and 3:7 by weight.  
     
     
         7 . A preparation according to  claim 1 , wherein the poloxamers are selected from the group consisting of P188, P234, P237, P338 and P407.  
     
     
         8 . A preparation according to  claim 1 , wherein the poloxamers are P407 and P188.  
     
     
         9 . A preparation according to  claim 1 , wherein the poloxamer mixture forms between 3 and 15% w/v of the preparation.  
     
     
         10 . A preparation according to  claim 9 , wherein the poloxamer mixture forms between 5 and 10% w/v of the preparation.  
     
     
         11 . A preparation according to  claim 1 , consisting essentially of drug, poloxamers and water.  
     
     
         12 . A preparation according to  claim 1 , wherein the drug is 2-{4-3-(2-trifluoromethylphenothiazin-10-yl)propyl]piperazin-1-yl}ethyl decanoate.  
     
     
         13 . A preparation according to  claim 1 , wherein the drug is 2-{4-3-(2-trifluoromethylphenothiazin-10-yl)propyl]piperazin-1-yl}ethyl heptanoate.  
     
     
         14 . A preparation according to  claim 1 , wherein the drug is 2-methyl-5-(1-methylethyl)phenol.  
     
     
         15 . A preparation according to  claim 14 , wherein said preparation is suitable for topical administration.  
     
     
         16 . A preparation according to  claim 1 , wherein said drug is a local anaesthetic.  
     
     
         17 . A preparation according to  claim 16 , wherein the anaesthetic is selected from the group consisting of procaine, prilocaine, chloroprocaine, etidocaine, mepivacaine, lidocaine and lignocaine.  
     
     
         18 . A preparation according to  claim 17 , wherein the anaesthetic is 2-diethylamino-2′,6′-acetoxylidide (lidocaine) freebase.  
     
     
         19 . A preparation according to  claim 17 , wherein said preparation is suitable for topical administration.  
     
     
         20 . A preparation according to  claim 1 , further comprising a local anaesthetic.  
     
     
         21 . A preparation according to  claim 1 , wherein said preparation is a liquid.  
     
     
         23 . A preparation according to  claim 1 , wherein said preparation is a mobile gel or cream.  
     
     
         24 . A unit dose formulation comprising a preparation according to  claim 1 , wherein said preparation comprises a therapeutically effective amount of drug.  
     
     
         25 . A multiple unit dose formulation according to  claim 24 .  
     
     
         26 . A formulation according to  claim 24 , provided in a sealed container.  
     
     
         27 . A method for the prophylaxis or treatment of a subject in need thereof, said method comprising administration of an effective amount of the preparation of  claim 1  said subject.