Extended-release drug delivery compositions

Abstract

An extended-release drug delivery composition and method of administering the same is provided. The composition comprises microspheres loaded with a biologically-active agent and suspended in a soluble polymer capable of forming a film upon injection onto a biological surface.

What is claimed is: 
     
         1 . A pharmaceutical composition for an injection comprising:
 a) a biologically-active agent;   b) a film-forming agent comprising polyvinyl alcohol (PVA) in a carrier liquid; and   c) a surfactant;   
       wherein the carrier liquid is capable of evaporating at 37° C.; 
       wherein the PVA is in an amount from about 0.5% to about 10% w/v of the pharmaceutical composition; 
       wherein the PVA has a molecular weight of about 20,000 to about 30,000 Daltons; 
       wherein the biologically-active agent is suspended in the film-forming agent; 
       wherein the surfactant is in an amount from about 0.5% to about 5% w/v of the pharmaceutical composition; and 
       wherein the surfactant is selected from the group consisting of polysorbate 20, polysorbate 60, polysorbate 80, and sorbitan laurate. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the PVA is in an amount of about 10% w/v of the pharmaceutical composition. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the PVA is about 88% hydrolyzed. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the carrier liquid is selected from the group consisting of water, ethanol, benzyl alcohol, and ethyl acetate. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the carrier liquid is water. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the biologically-active agent is siRNA, DNA, an antibody, a protein, an antibiotic, an antiviral, or a steroid. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the biologically-active agent is betamethasone, dexamethasone, or penicillin. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition comprises a plurality of microspheres, wherein the plurality of microspheres comprises the biologically-active agent, and wherein the plurality of microspheres is suspended in the film-forming agent. 
     
     
         9 . The pharmaceutical composition of  claim 8 , wherein the plurality of microspheres was collected, filtered, and lyophilized prior to suspending the plurality of microspheres in the film-forming agent. 
     
     
         10 . The pharmaceutical composition of  claim 8 , wherein at least 90% of the plurality of microspheres have a particle diameter that does not deviate more than 10% from a mean particle diameter of the plurality of microspheres. 
     
     
         11 . The pharmaceutical composition of  claim 8 , wherein a mean particle diameter of the plurality of microspheres is less than 150 μm. 
     
     
         12 . The pharmaceutical composition of  claim 11 , wherein the mean particle diameter is from about 30 μm to about 60 μm. 
     
     
         13 . The pharmaceutical composition of  claim 8 , wherein the plurality of microspheres comprises poly (D,L-lactic-co-glycolic acid) (PLGA), poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(caprolactone) (PCL), poly(ethylene glycol) (PEG), poly(vinyl acetate) (PVAc), ethyl cellulose, or combinations thereof. 
     
     
         14 . The pharmaceutical composition of  claim 8 , wherein the plurality of microspheres comprises poly(D,L-lactic-co-glycolic acid) (PLGA). 
     
     
         15 . A pharmaceutical composition for an injection comprising:
 a) a biologically-active agent; and   b) a film-forming agent comprising polyvinyl alcohol (PVA) in a carrier liquid;   
       wherein the carrier liquid is capable of evaporating at 37° C.; 
       wherein the PVA is in an amount from about 0.5% to about 10% w/v of the pharmaceutical composition; 
       wherein the PVA has a molecular weight of about 20,000 to about 30,000 Daltons; and 
       wherein the biologically-active agent is suspended in the film-forming agent. 
     
     
         16 . A pharmaceutical composition for an injection comprising:
 a) a biologically-active agent; and   b) a film-forming agent comprising polyvinyl alcohol (PVA) in a carrier liquid; and   c) a plurality of microspheres;   
       wherein the carrier liquid is capable of evaporating at 37° C.; 
       wherein the PVA is in an amount from about 0.5% to about 10% w/v of the pharmaceutical composition; 
       wherein the PVA has a molecular weight of about 20,000 to about 30,000 Daltons; 
       wherein the plurality of microspheres comprises the biologically-active agent; and 
       wherein the plurality of microspheres is suspended in the film-forming agent. 
     
     
         17 . The pharmaceutical composition of  claim 16 , wherein the plurality of microspheres comprises poly(D,L-lactic-co-glycolic acid) (PLGA). 
     
     
         18 . The pharmaceutical composition of  claim 16 , further comprising a surfactant, wherein the surfactant is in an amount from about 0.5% to about 5% w/v of the pharmaceutical composition. 
     
     
         19 . The pharmaceutical composition of  claim 18 , wherein the surfactant is selected from the group consisting of polysorbate 20, polysorbate 60, polysorbate 80, and sorbitan laurate.