Self-emulsifying formulations of cholesteryl ester transfer protein inhibitors

Abstract

CETP Inhibitors have improved solubility and bioavailability in a lipophilic vehicle comprising a digestible oil, a lipophilic solvent, or a surfactant. Preferred such compositions are self-emulsifying or self-microemulsifying, and comprise 1. a CETP inhibitor; 2. a cosolvent; 3. a surfactant having an HLB of 1 to 8; 4. a surfactant having an HLB of over 8 to 20; and 5. optionally, a digestible oil.

1 - 51 . (canceled)  
   
   
       52 . A composition comprising: 
 5-25% of a compound which is 3-[[3-(4-chloro-3-ethylphenoxy)phenyl][3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol; 
 20-35% of a lipophilic solvent comprising triacetin or ethyl lactate;  
 10-35% of a high HLB surfactant comprising a non-ionic surfactant with a hydrophilic-lipophilic balance value from about 8 to 20 wherein said high HLB surfactant comprises polysorbate 80 or a polyethylene hydrogenated castor oil;  
 10-35% of a low HLB surfactant comprising a non-ionic surfactant with a hydrophilic-lipophilic balance value from about 1 to 8 wherein said low HLB surfactant comprises a mixture of mono- and diglycerides of capric and caprylic acids; and  
 10-25% of a digestible oil wherein said digestible oil comprises a medium chain triglyceride, wherein each of the three hydrocarbon chains therein is C6-C12.  
   
   
   
       53 . A composition as claimed in  claim 52 , which comprises, by weight: 
 8-12% of;    10-20% of said digestible oil;    25-35% of said lipophilic solvent which comprises triacetin:    10-30% of said high HLB surfactant which comprises polysorbate 80; and    15-35% of said low HLB surfactant which comprises a mixture of medium chain mono- and di-glycerides.    
   
   
       54 . A composition as claimed in  claim 52 , which comprises, by weight: 
 8-12% of    10-20% of said digestible oil;    25-35% of said lipophilic solventwhich comprises triacetin;    10-30% of said high HLB surfactant which comprises a polyethylene (40) hydrogenated castor oil;    15-35% of said low HLB surfactant which comprises a mixture of medium chain mono- and di-glycerides.    
   
   
       55 . A composition as claimed in  claim 52 , which comprises, by weight: 
 8-25% of [2R, 4S]4-[(3,5-Bis-trifluoromethyl-benzyl)methoxycarbonyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester;    10-25% of digestible oil;    20-35% of said lipophilic solvent which comprises triacetin;    10-30% of said high HLB surfactant which comprises polysorbate 80; and    15-35% of said low HLB surfactant which comprises a mixture of medium chain mono- and di-glycerides.