Compositions and methods involving polymer, solvent and high viscosity liquid carrier material

Abstract

Compositions may include a pharmaceutical active agent, a high viscosity liquid carrier material (HVLCM), a lactic acid-based polymer, and an organic solvent. Related compositions and methods are also disclosed. For instance, a carrier formulation for controlled release of injectable drugs is disclosed. The formulation may include a non-water soluble high viscosity liquid which may be sucrose acetate isobutyrate, a lactic-acid based polymer which may be a poly(lactic acid)(glycolic acid), and an organic solvent which maintains the composition in a monophasic form at 25° C. in one atmosphere. Drug in the formulation may be released upon administration such that less than 10% (e.g. 2-8%) of drug is released in the first 5 hours; 10% to 80% of the drug is released during a period of 5 hours to 7 days after administration; and 10% to 40% of the drug is released gradually over a period of 7 days to 28 days from initial administration. The drug may be an anti-schizophrenia agent delivered by injection.

1 - 23 . (canceled) 
     
     
         24 . A composition comprising:
 0.5 wt % to 10 wt %, based on total weight of the composition, of particles comprising a chemotherapeutic agent;   30 wt % to 60 wt %, based on total weight of the composition, of sucrose acetate isobutyrate;   10 wt % to 35 wt %, based on total weight of the composition, of a lactic acid-based polymer initiated with one of dodecanol and lactic acid, the polymer having a lactic acid to glycolic acid molar ratio ranging from 100:0 to 40:60; and   10 wt % to 50 wt %, based on total weight of the composition, of an organic solvent comprising at least one member selected from N-methyl-pyrrolidone, propylene carbonate, ethanol, benzyl alcohol, and benzyl benzoate.   
     
     
         25 . The composition of  claim 24 , wherein the chemotherapeutic agent is present in an amount ranging from 1 wt % to 5 wt %, based on total weight of the composition. 
     
     
         26 . The composition of  claim 24 , wherein the particles having a median particle size, as measured by laser diffraction, ranging from 0.1 micrometer to 100 micrometers. 
     
     
         27 . The composition of  claim 24 , wherein the particles have a median particle size, as measured by laser diffraction, ranging from 0.2 micrometer to 50 micrometers. 
     
     
         28 . The composition of  claim 24 , the particles have a median particle size, as measured by laser diffraction, ranging from 0.25 micrometer to 50 micrometers. 
     
     
         29 . The composition of  claim 24 , wherein the sucrose acetate isobutyrate is present in the composition in an amount ranging from 30 wt % to 55 wt %, based on total weight of the composition. 
     
     
         30 . The composition of  claim 24 , wherein the lactic acid-based polymer is present in the composition in an amount ranging from 15 wt % to 25 wt %, based on total weight of the composition. 
     
     
         31 . The composition of  claim 24 , wherein the lactic acid-based polymer has a lactic acid to glycolic acid molar ratio ranging from 95:5 to 60:40. 
     
     
         32 . The composition of  claim 24 , wherein the lactic acid-based polymer has a weight average molecular weight ranging from 4000 Daltons to 30,000 Daltons 
     
     
         33 . The composition of  claim 24 , wherein the lactic acid-based polymer has a weight average molecular weight ranging from 15,000 Daltons to 30,000 Daltons. 
     
     
         34 . The composition of  claim 24 , wherein the organic solvent is present in the composition in an amount ranging from 20 wt % to 40 wt %, based on total weight of the composition. 
     
     
         35 . The composition of  claim 24 , wherein a weight ratio of the sucrose acetate isobutyrate to the lactic acid-based polymer to the organic solvent ranges from 1:0.066-1.3:0.3-1.7. 
     
     
         36 . The composition of  claim 24 , wherein when the composition is administered subcutaneously as a single dose to a human patient, a median amount of pharmaceutical active agent released from the composition provides an AUC(0 to 1 day) that is less than 20% of AUC(0 to 28 days). 
     
     
         37 . The composition of  claim 25 , wherein when the composition is administered subcutaneously as a single dose to a human patient, a median amount of pharmaceutical active agent released from the composition provides an AUC(0 to 1 day) that is less than 20% of AUC(0 to 28 days). 
     
     
         38 . The composition of  claim 29 , wherein when the composition is administered subcutaneously as a single dose to a human patient, a median amount of pharmaceutical active agent released from the composition provides an AUC(0 to 1 day) that is less than 20% of AUC(0 to 28 days). 
     
     
         39 . The composition of  claim 24 , wherein the composition has a viscosity of less than 3000 cP at a shear rate of 100 s −1  at 25° C. 
     
     
         40 . The composition of  claim 25 , wherein the composition has a viscosity of less than 3000 cP at a shear rate of 100 s −1  at 25° C. 
     
     
         41 . The composition of  claim 29 , wherein the composition has a viscosity of less than 3000 cP at a shear rate of 100 s −1  at 25° C. 
     
     
         42 . The composition of  claim 30 , wherein the composition has a viscosity of less than 3000 cP at a shear rate of 100 s −1  at 25° C. 
     
     
         43 . The composition of  claim 34 , wherein the composition has a viscosity of less than 3000 cP at a shear rate of 100 s −1  at 25° C.