Spontaneously dispersible N-benzoyl staurosporine compositions

Abstract

Spontaneously dispersible N-benzoyl-staurosporine compositions are discussed for oral administration having high bioavailability levels and reduced variability of bioavailability levels of N-benzoyl-staurosporine, as well as their preparation and use in medical treatment.

1 . A spontaneously dispersible pharmaceutical composition for oral administration comprising 
 1) N-benzoyl-staurosporine,    2) a hydrophilic component, and    2) a surfactant.    
     
     
         2 . A composition as claimed in  claim 1  further comprising a lipophilic component.  
     
     
         3 . A composition as claimed in  claim 1  or  claim 2  wherein the hydrophilic component comprises ethanol, 1,2-propylene glycol or a polyethylene glycol.  
     
     
         4 . A composition as claimed in any preceding claim wherein the surfactant is selected from the group consisting of polyoxyethylenes, polyglycerols and related polyols, and polyalkylene oxide copolymers.  
     
     
         5 . A composition as claimed in any preceding claim wherein the surfactant is selected from the group consisting of a polyoxyethylene castor oil, a polyoxyethylene alkyl ether, and a polysorbate.  
     
     
         6 . A composition as claimed in any preceding claim wherein the surfactant has an HLB value of greater than 10 and the composition further comprises a co-surfactant having an HLB value of less than 10.  
     
     
         7 . A composition as claimed in  claim 6  wherein the surfactant is selected from the group consisting of a polyoxyethylene castor oil, a polyoxyethylene alkyl ether, and a polysorbate, and the co-surfactant comprises a transesterified ethoxylated vegetable oil.  
     
     
         8 . A composition as claimed in  claim 2  wherein the surfactant has an HLB value of greater than 10 and the lipophilic component comprises a fatty acid glyceride.  
     
     
         9 . A spontaneously dispersible pharmaceutical composition for oral administration comprising 
 (a) up to 20% by weight of N-benzoyl-staurosporine,    (b) 5 to 50% by weight of a hydrophilic component,    (c) 5 to 80% of a surfactant or surfactant mixture,    (d) 5 to 85% of a lipophilic component, and    (e) 0.05 to 5% of an additive.    
     
     
         10 . A method of treatment for treating subjects in need of N-benzoyl-staurosporine therapy comprising administering a dispersible pharmaceutical composition according to any preceeding claim to a subject in need of such treatment.  
     
     
         11 . A pharmaceutical composition for oral administration comprising N-benzoylstaurosporine and having 
 (a) a variability of bioavailability levels of N-benzoylstaurosporine of from 5 to 17%;    (b) an AUC (0-48 h)/dose value (in (h.nmol/L)/(mg/kg)) of from 380 to 2000, or    (c) a C max /dose value (in (nmol/L)/(mg/kg)) of from 60 to 310, upon administration of a dose (in mg/kg) of N-benzoylstaurosporine to fasted beagle dogs.    
     
     
         12 . A method of increasing bioavailability levels or reducing variability of bioavailability levels of N-benzoylstaurosporine by mixing N-benzoylstaurosporine with a carrier comprising a hydrophilic component, and a surfactant.  
     
     
         13 . A method of increasing bioavailability levels or reducing variability of bioavailability levels of N-benzoylstaurosporine, said method comprising orally administering a composition according to any preceding claim to fasted beagle dogs.