Depot Formulations

Abstract

Disclosed are formulations and related methods that comprise a non-polymeric, non-water soluble high viscosity liquid carrier material having a viscosity of at least 5,000 cP at 37° C. that does not crystallize neat under ambient or physiological conditions; a specified linear polymer comprising lactide repeat units; and one or more solvents that have a solvent capacity.

What is claimed is: 
     
         1 . A formulation comprising:
 (i) a non-polymeric, non-water soluble high viscosity liquid carrier material having a viscosity of at least 5,000 cP at 37° C. that does not crystallize neat under ambient or physiological conditions;   (ii) a linear polymer comprising lactide repeat units, wherein the linear polymer possesses a ratio R of lactide repeat units to total repeat units in the linear polymer; and   (iii) one or more solvents that have a solvent capacity;   wherein the linear polymer has a weight average molecular weight less than or equal to about 15,000 Daltons, and   wherein
 (a) R satisfies the following: about 0.55≦R≦about 0.95; 
 (b) when R satisfies the following: about 0.55≦R≦0.85, the solvent capacity of the one or more solvents is greater than or equal to about 20%; and 
 (c) when R satisfies the following: greater than about 0.85 to about 0.95, the solvent capacity of the one or more solvents is greater than or equal to about 10%. 
   
     
     
         2 . The formulation of  claim 1 , wherein when R satisfies the following: about 0.55≦R≦0.85, the solvent capacity of the one or more solvents is greater than or equal to about 25%; and when R satisfies the following: greater than about 0.85 to about 0.95, the solvent capacity of the one or more solvents is greater than or equal to about 15%. 
     
     
         3 . The formulation of  claim 2 , wherein: wherein when R satisfies the following: about 0.55≦R≦0.85, the solvent capacity of the one or more solvents is greater than or equal to about 35%; and when R satisfies the following: greater than about 0.85 to about 0.95, the solvent capacity of the one or more solvents is greater than or equal to about 25%. 
     
     
         4 . The formulation of  claim 1 , wherein the non-polymeric, non-water soluble high viscosity liquid carrier material having a viscosity of at least 5,000 cP at 37° C. that does not crystallize neat under ambient or physiological conditions comprises sucrose acetate isobutyrate. 
     
     
         5 . The formulation of  claim 1 , further comprising a biologically active substance. 
     
     
         6 . The formulation of  claim 5 , wherein the biologically active substance comprises an atypical antipsychotic. 
     
     
         7 . The formulation of  claim 6 , wherein the atypical antipsychotic comprises risperidone or a pharmaceutically acceptable salt or polymorph thereof. 
     
     
         8 . The formulation of  claim 1 , wherein the linear polymer comprises poly (lactide-co-glycolide). 
     
     
         9 . The formulation of  claim 1 , wherein the linear polymer is present in an amount ranging from about 1 wt % to about 45 wt %, based on the total weight of the formulation. 
     
     
         10 . The formulation of  claim 9 , wherein the linear polymer is present in an amount ranging from about 15 wt % to about 45 wt %, based on the total weight of the formulation. 
     
     
         11 . A formulation comprising:
 (i) a non-polymeric, non-water soluble high viscosity liquid carrier material having a viscosity of at least 5,000 cP at 37° C. that does not crystallize neat under ambient or physiological conditions;   (ii) a linear polymer comprising lactide repeat units, wherein the linear polymer possesses a ratio R of lactide repeat units to total repeat units in the linear polymer; and   (iii) one or more solvents that have a solvent capacity;   wherein the linear polymer has a weight average molecular weight less than or equal to about 15,000 Daltons, and   wherein:
 (a) R satisfies the following: about 0.55≦R≦0.85; and 
 (b) the solvent capacity of the one or more solvents is greater than or equal to about 20%. 
   
     
     
         12 . The formulation of  claim 11 , the solvent capacity of the one or more solvents is greater than or equal to about 25%. 
     
     
         13 . The formulation of  claim 12 , the solvent capacity of the one or more solvents is greater than or equal to about 35%. 
     
     
         14 . The formulation of  claim 11 , wherein the non-polymeric, non-water soluble high viscosity liquid carrier material having a viscosity of at least 5,000 cP at 37° C. that does not crystallize neat under ambient or physiological conditions comprises sucrose acetate isobutyrate. 
     
     
         15 . The formulation of  claim 11 , further comprising a biologically active substance. 
     
     
         16 . The formulation of  claim 15 , wherein the biologically active substance comprises an atypical antipsychotic. 
     
     
         17 . The formulation of  claim 16 , wherein the atypical antipsychotic comprises risperidone or a pharmaceutically acceptable salt or polymorph thereof. 
     
     
         18 . The formulation of  claim 11 , wherein the linear polymer comprises poly (lactide-co-glycolide). 
     
     
         19 . The formulation of  claim 11 , wherein the linear polymer is present in an amount ranging from about 1 wt % to about 45 wt %, based on the total weight of the formulation. 
     
     
         20 . The formulation of  claim 19 , wherein the linear polymer is present in an amount ranging from about 15 wt % to about 45 wt %, based on the total weight of the formulation. 
     
     
         21 . A formulation comprising:
 (i) a non-polymeric, non-water soluble high viscosity liquid carrier material having a viscosity of at least 5,000 cP at 37° C. that does not crystallize neat under ambient or physiological conditions;   (ii) a linear polymer comprising lactide repeat units, wherein the linear polymer possesses a ratio R of lactide repeat units to total repeat units in the linear polymer; and   (iii) one or more solvents that have a solvent capacity;   wherein the linear polymer has a weight average molecular weight less than or equal to about 15,000 Daltons, and   wherein
 (a) R satisfies the following: greater than about 0.85 to about 0.95; and 
 (b) the solvent capacity of the one or more solvents is greater than or equal to about 10%. 
   
     
     
         22 . The formulation of  claim 21 , wherein the solvent capacity of the one or more solvents is greater than or equal to about 15%. 
     
     
         23 . The formulation of  claim 22 , wherein the solvent capacity of the one or more solvents is greater than or equal to about 25%. 
     
     
         24 . The formulation of  claim 21 , wherein the non-polymeric, non-water soluble high viscosity liquid carrier material having a viscosity of at least 5,000 cP at 37° C. that does not crystallize neat under ambient or physiological conditions comprises sucrose acetate isobutyrate. 
     
     
         25 . The formulation of  claim 21 , further comprising a biologically active substance. 
     
     
         26 . The formulation of  claim 21 , wherein the biologically active substance comprises an atypical antipsychotic. 
     
     
         27 . The formulation of  claim 26 , wherein the atypical antipsychotic comprises risperidone or a pharmaceutically acceptable salt or polymorph thereof. 
     
     
         28 . The formulation of  claim 21 , wherein the linear polymer comprises poly (lactide-co-glycolide). 
     
     
         29 . The formulation of  claim 21 , wherein the linear polymer is present in an amount ranging from about 1 wt % to about 45 wt %, based on the total weight of the formulation. 
     
     
         30 . The formulation of  claim 29 , wherein the linear polymer is present in an amount ranging from about 15 wt % to about 45 wt %, based on the total weight of the formulation. 
     
     
         31 . A formulation comprising:
 (i) a non-polymeric, non-water soluble high viscosity liquid carrier material having a viscosity of at least 5,000 cP at 37° C. that does not crystallize neat under ambient or physiological conditions;   (ii) a linear polymer comprising lactide repeat units, wherein the linear polymer possesses a ratio R of lactide repeat units to total repeat units in the linear polymer, wherein R satisfies the following: about 0.55≦R≦about 0.95; and   (iii) one or more solvents present in an amount ranging from about one weight percent up to about 35 weight percent, based on the total weight of the formulation;   wherein the linear polymer has a weight average molecular weight less than or equal to about 15,000 Daltons, and   wherein the one or more solvents comprise ethanol, ethyl lactate, propylene carbonate, glycofurol, N-methylpyrrolidone, 2-pyrrolidone, benzyl benzoate, miglyol, propylene glycol, acetone, methyl acetate, ethyl acetate, methyl ethyl ketone, benzyl alcohol, triacetin, dimethylformamide, dimethylsulfoxide, tetrahydrofuran, caprolactam, decylmethylsulfoxide, oleic acid, and/or 1-dodecylazacycloheptan-2-one, and combinations of any of the above.   
     
     
         32 . The formulation of  claim 31 , wherein the non-polymeric, non-water soluble high viscosity liquid carrier material having a viscosity of at least 5,000 cP at 37° C. that does not crystallize neat under ambient or physiological conditions comprises sucrose acetate isobutyrate. 
     
     
         33 . The formulation of  claim 31 , further comprising a biologically active substance. 
     
     
         34 . The formulation of  claim 33 , wherein the biologically active substance comprises an atypical antipsychotic. 
     
     
         35 . The formulation of  claim 34 , wherein the atypical antipsychotic comprises risperidone or a pharmaceutically acceptable salt or polymorph thereof. 
     
     
         36 . The formulation of  claim 31 , wherein the linear polymer comprises poly (lactide-co-glycolide). 
     
     
         37 . The formulation of  claim 31 , wherein the one or more solvents are present in an amount ranging from about one weight percent up to about 30 weight percent, based on the total weight of the formulation. 
     
     
         38 . The formulation of  claim 37 , wherein the one or more solvents are present in an amount ranging from about one weight percent up to about 25 weight percent, based on the total weight of the formulation. 
     
     
         39 . The formulation of  claim 31 , wherein the linear polymer is present in an amount ranging from about 1 wt % to about 45 wt %, based on the total weight of the formulation. 
     
     
         40 . The formulation of  claim 39 , wherein the linear polymer is present in an amount ranging from about 15 wt % to about 45 wt %, based on the total weight of the formulation.