Preparation of injectable suspensions having improved injectability

Abstract

Injectable compositions having improved injectability. The injectable compositions include microparticles suspended in an aqueous injection vehicle having a viscosity of at least 20 cp at 20° C. The increased viscosity of the injection vehicle that constitutes the fluid phase of the suspension significantly reduces in vivo injectability failures. The injectable compositions can be made by mixing dry microparticles with an aqueous injection vehicle to form a suspension, and then mixing the suspension with a viscosity enhancing agent to increase the viscosity of the fluid phase of the suspension to the desired level for improved injectability.

What is claimed is: 
     
         1 . A composition for injection through a needle into a host, consisting of:
 microparticles comprising a peptide and a polymeric binder selected from the group consisting of poly(glycolic acid), poly-d,l-lactic acid, poly-l-lactic acid, copolymers of the foregoing, poly(aliphatic carboxylic acids), copolyoxalates, polycaprolactone, polydioxanone, poly(ortho carbonates), poly(acetals), poly(lactic acid-caprolactone), polyorthoesters, poly(glycolic acid-caprolactone), polyanhydrides, and polyphosphazines; and   an injection vehicle, wherein the injection vehicle consists essentially of a viscosity enhancing agent, a wetting agent, and a tonicity adjusting agent,   wherein the microparticles are suspended in the injection vehicle at a concentration of more than about 30 mg/ml and up to about 300 mg/ml to form a suspension, wherein a fluid phase of the suspension has a viscosity of greater than 30 cP and less than 600 cP at 20° C., and wherein the viscosity of the fluid phase of the suspension provides injectability of the composition into the host through a needle of medically acceptable size.   
     
     
         2 . The composition of  claim 1 , wherein the polymeric binder is a copolymer of poly(glycolic acid) and poly-d,l-lactic acid. 
     
     
         3 . The composition of  claim 1 , wherein the viscosity enhancing agent is sodium carboxymethyl cellulose. 
     
     
         4 . The composition of  claim 1 , wherein the wetting agent is selected from the group consisting of polysorbate 20, polysorbate 40, and polysorbate 80. 
     
     
         5 . The composition of  claim 1 , wherein the tonicity adjusting agent is sodium chloride. 
     
     
         6 . The composition of  claim 1 , wherein the injection vehicle consists essentially of sodium carboxymethyl cellulose, polysorbate 20, and sodium chloride. 
     
     
         7 . The composition of  claim 1 , wherein a mass median diameter of the microparticles is less than about 250 μm. 
     
     
         8 . The composition of  claim 7 , wherein the mass median diameter of the microparticles is in the range of from about 20 μm to about 150 μm. 
     
     
         9 . The composition of  claim 1 , wherein the polymeric binder is poly(lactide-co-glycolide), and the injection vehicle comprises sodium carboxymethyl cellulose, polysorbate 20, and sodium chloride. 
     
     
         10 . The composition of  claim 9 , wherein a mass median diameter of the microparticles is less than about 250 μm. 
     
     
         11 . The composition of  claim 10 , wherein the mass median diameter of the microparticles is in the range of from about 20 μm to about 150 μm. 
     
     
         12 . The composition of  claim 1 , wherein the polymeric binder is poly(d,l-lactide-co-glycolide) having a molar ratio of lactide to glycolide in the range of from about 85:15 to about 50:50. 
     
     
         13 . The composition of  claim 1 , wherein the viscosity of the fluid phase of the suspension provides injectability of the composition into the host through a needle ranging in diameter from 18-22 gauge. 
     
     
         14 . The composition of  claim 1 , wherein the injection vehicle is aqueous.