Solvent/polymer solutions as suspension vehicles

Abstract

A nonaqueous, single-phase vehicle that is capable of suspending an active agent. The nonaqueous, single-phase vehicle includes at least one solvent and at least one polymer and is formulated to exhibit phase separation upon contact with an aqueous environment. The at least one solvent may be selected from the group consisting of benzyl benzoate, decanol, ethyl hexyl lactate, and mixtures thereof and the at least one polymer may be selected from the group consisting of a polyester, pyrrolidone, ester of an unsaturated alcohol, ether of an unsaturated alcohol, polyoxyethylenepolyoxypropylene block copolymer, and mixtures thereof. In one embodiment, the at least one solvent is benzyl benzoate and the at least one polymer is polyvinylpyrrolidone. A stable, nonaqueous suspension formulation that includes the nonaqueous, single-phase vehicle and an active agent, and a method of forming the same, are also disclosed.

1 - 7 . (canceled) 
     
     
         8 . A stable, nonaqueous suspension formulation, comprising:
 a particle formulation comprising an active agent, wherein the active agent comprises a peptide, polypeptide, or protein; and   a nonaqueous, single-phase vehicle consisting essentially of about 40% to 60% (w/w) polyvinylpyrrolidone and about 40% to 60% (w/w) of solvent, wherein the solvent is either lauryl alcohol or lauryl lactate.   
     
     
         9 - 25 . (canceled) 
     
     
         26 . The suspension formulation of  claim 8 , wherein the polyvinylpyrrolidone is about 50% (w/w) and the solvent is about 50% (w/w), wherein the solvent is lauryl lactate. 
     
     
         27 . The suspension formulation of  claim 8 , wherein the polyvinylpyrrolidone is about 55% (w/w) and the solvent is about 45% (w/w), wherein the solvent is lauryl alcohol. 
     
     
         28 . The suspension formulation of  claim 8 , wherein the particle formulation further comprises a sugar, methionine, and a buffer. 
     
     
         29 . The suspension formulation of  claim 28 , wherein the sugar is sucrose. 
     
     
         30 . The suspension formulation of  claim 28 , wherein the buffer is citrate. 
     
     
         31 . The suspension formulation of  claim 28 , wherein the sugar is sucrose, and the buffer is citrate. 
     
     
         32 . The suspension formulation of  claim 8 , wherein the particle formulation is formed by lyophilization, spray-drying, or freeze-drying. 
     
     
         33 . The suspension formulation of  claim 8 , wherein the particle formulation is present in the suspension formulation in a range from approximately 0.1 to 50 wt %. 
     
     
         34 . The suspension formulation of  claim 8 , wherein the particle formulation is present in the suspension formulation in a range from approximately 3 to 12 wt %. 
     
     
         35 . The suspension formulation of  claim 8 , wherein the vehicle has a viscosity of between approximately 5,000 poise to approximately 50,000 poise. 
     
     
         36 . The suspension formulation of  claim 8 , wherein the nonaqueous, single-phase vehicle exhibits phase separation upon contact with an aqueous environment having less than approximately 10% water. 
     
     
         37 . An implantable osmotic drug delivery device, comprising
 a reservoir containing the suspension formulation of  claim 8 , and   an orifice through which the active agent is delivered.   
     
     
         38 . A stable, nonaqueous suspension formulation, comprising:
 a particle formulation comprising (i) a peptide, polypeptide, or protein, (ii) sucrose, (iii) methionine, and (iv) citrate buffer; and   a nonaqueous, single-phase vehicle consisting essentially of about 40% to 60% (w/w) polyvinylpyrrolidone and about 40% to 60% (w/w) of solvent, wherein the solvent is either lauryl alcohol or lauryl lactate.   
     
     
         39 . The suspension formulation of  claim 38 , wherein the polyvinylpyrrolidone is about 50% (w/w) and the solvent is about 50% (w/w), wherein the solvent is lauryl lactate. 
     
     
         40 . The suspension formulation of  claim 38 , wherein the polyvinylpyrrolidone is about 55% (w/w) and the solvent is about 45% (w/w), wherein the solvent is lauryl alcohol. 
     
     
         41 . The suspension formulation of  claim 38 , wherein the particle formulation is formed by lyophilization, spray-drying, or freeze-drying. 
     
     
         42 . The suspension formulation of  claim 38 , wherein the particle formulation is present in the suspension formulation in a range from approximately 0.1 to 50 wt %. 
     
     
         43 . The suspension formulation of  claim 38 , wherein the particle formulation is present in the suspension formulation in a range from approximately 3 to 12 wt %. 
     
     
         44 . The suspension formulation of  claim 38 , wherein the vehicle has a viscosity of between approximately 5,000 poise to approximately 50,000 poise. 
     
     
         45 . The suspension formulation of  claim 38 , wherein the nonaqueous, single-phase vehicle exhibits phase separation upon contact with an aqueous environment having less than approximately 10% water. 
     
     
         46 . An implantable osmotic drug delivery device, comprising
 a reservoir containing the suspension formulation of  claim 38 , and   an orifice through which the active agent is delivered.