Injectable sustained release delivery devices

Abstract

An injectable drug delivery device includes a core containing one or more drugs and one or more polymers. The core may be surrounded by one or more polymer outer layers (referred to herein as “coatings,” “skins,” or “outer layers”). In certain embodiments, the device is formed by extruding or otherwise preforming a polymeric skin for a drug core. The drug core may be co-extruded with the skin, or inserted into the skin after the skin has been extruded, and possibly cured. In other embodiments, the drug core may be coated with one or more polymer coatings. These techniques may be usefully applied to fabricate devices having a wide array of drug formulations and skins that can be selected to control the release rate profile and various other properties of the drugs in the drug core in a form suitable for injection using standard or non-standard gauge needles. The device may be formed by combining at least one polymer, at least one drug, and at least one liquid solvent to form a liquid suspension or solution wherein, upon injection, such suspension or solution under goes a phase change and forms a gel. The configuration may provide for controlled release of the drug(s) for an extended period.

1 . A drug delivery device shaped and sized for injection comprising: 
 a core including one or more drugs; and    a polymeric skin at least partially surrounding the core, the skin comprising a first one or more polymers.    
     
     
         2 . The device of  claim 1 , further characterized by one or more of: 
 A) the core comprises a matrix of the one or more drugs and a second one or more polymers,    B) the one or more drugs includes at least one of a codrug or a prodrug,    C) the core comprises a biocompatible gelling formulation,    D) the one or more drugs includes a steroid,    E) at least one of the one or more drugs comprises an anti-metabolite,    F) at least one of the one or more drugs comprises an adrenergic agent,    G) at least one of the one or more drugs comprises a carbonic anhydrase inhibitor,    H) at least one of the one or more drugs comprises an antiviral agent,    I) the polymeric skin is one of impermeable, semi-permeable, or permeable to at least one of the one or more drugs,    J) the polymeric skin comprises at least one of PVAC, PCL, PEG, PLGA, EVA, PVA,    PLA, PGA, polyalkyl cyanoacralate, polyurethane, or nylon, or a copolymer thereof,    K) the polymeric skin further comprises at least one drug,    L) the device is shaped and sized for injection through at least one of a needle having a size from about 30 gauge to about 15 gauge or a cannula having a size from about 30 gauge to about 15 gauge,    M) the device is shaped and sized for injection through at least one of a cannula having a size from about 30 gauge to about 15 gauge or a needle having a size from about 30 gauge to about 15 gauge,    N) the device is shaped and sized for at least one of periocular or intraocular injection,    O) the device further comprises an anchor for securing the device after injection, and    P) the device provides sustained release of the one or more drugs when exposed to a biological medium.    
     
     
         3 . The device of  claim 2 , further characterized by one or more of: 
 A) at least one of the second one or more polymers is bioerodible,    B) the second one or more polymers comprises at least one of poly(vinyl acetate) (PVAC), poly(caprolactone) (PCL), polyethylene glycol (PEG), poly(dl-lactide-co-glycolide) (PLGA), ethylene vinyl acetate polymer (EVA), poly(vinyl acetate) (PVA), poly(lactic acid) (PLA), poly(glycolic acid) (PGA), polyalkyl cyanoacralate, polyurethane, or nylon, or a copolymer thereof,    C) the steroid comprises at least one of loteprednol etabonate, triamcinolone acetonide (TA), fluocinolone acetonide, or anacortave acetate,    D) the anti-metabolite comprises 5-fluorouracil (5-FU),    E) the adrenergic agent comprises brimonidine,    F) the carbonic anhydrase inhibitor comprises at least one of acetazolamide, methazolamide, ethoxzolamide, dichlorphenamide, dorzolamide, or brinzolamide, or;    G) the antiviral agent comprises neviripine,    H) at least one of the first one or more polymers and the second one or more polymers is bioerodible,    I) at least one of the first one or more polymers and the second one or more polymers is radiation curable,    J) at least one of the first one or more polymers and the second one or more polymers is heat curable,    K) at least one of the first one or more polymers and the second one or more polymers is evaporation curable,    L) at least one of the first one or more polymers and the second one or more polymers is curable by catalyzation, and    M) the device further comprises a second polymeric skin.    
     
     
         4 - 30 . (canceled)  
     
     
         31 . The device of  claim 3 , further characterized by one or more of: 
 A) the polymeric skin has a different permeability to the one or more drugs than the second polymeric skin, and the core is completely covered by a combination of the polymeric skin and the second polymeric skin, or;    B) the second polymeric skin is bioerodible.    
     
     
         32 . (canceled)  
     
     
         33 . The device of  claim 31 , further characterized by one or more of: 
 A) a release rate of at least one of the one or more drugs is influenced by an erosion of at least one of the polymeric skin or the second polymeric skin,    B) a release rate of at least one of the one or more drugs is independent of an erosion of at least one of the polymeric skin or the second polymeric skin,    C) a release rate of at least one of the one or more drugs is controlled by at least one of the permeability of the second polymeric skin to the at least one of the one or more drugs and a surface area of the core that is not covered by the polymeric skin,    D) a release rate of at least one of the one or more drugs is controlled by at least one of the permeability of the second polymeric skin to the at least one of the one or more drugs and a surface area of the core that is not covered by the polymeric skin,    E) at least one of the polymeric skin and the second polymeric skin prevent direct interaction of biological fluids with the core,    F) a release rate of at least one of the one or more drugs is controlled by a surface area of the core,    G) a release rate of at least one of the one or more drugs is not substantially influenced by diffusion of the at least one drug through the core,    H) a release rate of at least one of the one or more drugs is significantly influenced by a solubility of the at least one drug within the core,    J) at least one of the one or more drugs is more stable within the device than in a biological medium,    K) the device provides increased stability of at least one of the one or more drugs to a curing process,    L) the device provides increased stability of at least one of the one or more drugs to storage, and    M) the device further comprises an anchor.    
     
     
         34 - 45 . (canceled)  
     
     
         46 . A method comprising: 
 extruding a polymeric skin;    extruding within the polymeric skin a core containing one or more drugs to provide a co-extruded mass having a core that includes the one or more drugs; and    forming the co-extruded mass into at least one drug delivery device shaped and sized for injection.    
     
     
         47 . The method of  claim 46 , further characterized by one or more of: 
 A) the polymeric skin includes at least one curable polymer, the method further comprising at least partially curing the polymeric skin,    B) the co-extruded mass includes segmenting the co-extruded mass into a plurality of segments,    C) forming the co-extruded mass includes segmenting the co-extruded mass into a plurality of tubular segments,    D) the polymeric skin includes at least one drug,    E) the method further comprises attaching an anchor to one of the at least one drug delivery devices, the anchor adapted to secure the drug delivery device after injection.    
     
     
         48 . The method of  claim 47 , further characterized by one or more of: 
 A) the at least one curable polymer is radiation curable, the method further comprising applying radiation to the polymeric skin,    B) the polymeric skin is cured at a curing station,    C) the method further comprises coating the plurality of segments with one or more layers including at least one of a layer that is permeable to the one or more drugs, a layer that is semi-permeable to the one or more drugs, or a layer that is bioerodible,    D) the method further comprises coating the plurality of segments using at least one of dip coating or film coating, and    E) a segmenting station is provided for segmenting the co-extruded mass.    
     
     
         49 - 56 . (canceled)  
     
     
         57 . The method of  claim 47  wherein attaching an anchor comprises: 
 applying an ultraviolet curable adhesive to the drug delivery device;    contacting the anchor to the ultraviolet curable adhesive; and    exposing the ultraviolet curable adhesive to ultraviolet radiation.    
     
     
         58 . A device comprising: 
 a drug core containing one or more drugs, the drug core having a substantially cylindrical shape with a side wall, a first end, and a second end;    a polymeric skin surrounding the side wall of the drug core and extending beyond at least the first end of the drug core to create a reservoir;    an adhesive within the reservoir; and    an anchor adapted to secure the device after injection, the anchor partially embedded within the adhesive.    
     
     
         59 . The device of  claim 58  wherein the adhesive is a curable adhesive.  
     
     
         60 . The device of  claim 59  wherein the adhesive is a radiation curable adhesive, or 
 the adhesive is an ultraviolet curable adhesive.    
     
     
         61 . (canceled)  
     
     
         62 . A method for forming an injectable drug delivery device comprising: 
 forming a polymeric skin having an interior region;    inserting a mixture into the interior region of the polymeric skin, the mixture including at least one drug;    segmenting the polymeric skin and mixture into one or more segments to provide one or more drug cores, each having a first end and a second end;    placing one of the drug cores into a polymeric sleeve that extends beyond at least the second end of the drug core to provide a reservoir; and    creating a diffusion membrane over the first end of the drug core, the diffusion membrane permeable to the at least one drug.    
     
     
         63 . The method of  claim 62  further comprising one or more of: 
 A) inserting a curable adhesive into the reservoir at the second end of the drug core;    placing a first portion of an anchor into the curable adhesive, a second portion of the anchor adapted to secure a drug delivery device in vivo; and 
 curing the curable adhesives  
   B) sterilizing the drug delivery device, and    C) packaging the drug delivery device for shipment.    
     
     
         64 - 65 . (canceled)  
     
     
         66 . A method comprising: 
 extruding a polymeric skin having an interior region;    inserting one or more drugs into the interior region to provide a substantially cylindrical mass having a core that includes the one or more drugs; and    forming the cylindrical mass into at least one drug delivery device shaped and sized for injection.    
     
     
         67 . The method of  claim 66  further comprising one or more of: 
 A) at least partially curing the polymeric skin before inserting one or more drug,    B) at least partially curing the cylindrical mass before forming the cylindrical mass, and    C) coating the at least one drug delivery device with a polymeric layer.    
     
     
         68 - 69 . (canceled)  
     
     
         70 . A method comprising: 
 inserting a wire into an uncured polymer;    curing the polymer;    withdrawing the wire from the polymer to obtain a polymeric skin surrounding a portion of the wire;    removing the polymeric skin from the wire;    inserting one or more drugs into an interior region of the polymeric skin to provide a substantially cylindrical mass having a core that includes the one or more drugs; and    forming the cylindrical mass into at least one drug delivery device shaped and sized for injection.    
     
     
         71 . The method of  claim 70 , further characterized by one or more of: 
 A) the polymer is polyimide,    B) the wire is a Nitinol wire, and    C) the one or more drugs comprises a drug matrix of at least one drug and at least one polymer.    
     
     
         72 - 73 . (canceled)  
     
     
         74 . A method for treating or reducing the risk of retroviral or lentiviral infection comprising injecting a sustained release drug delivery system including an antiviral agent in a patient in need of treatment wherein a dose of said agent is released for at least 7 days.  
     
     
         75 . A method for treating or reducing the risk of retroviral or lentiviral infection comprising injecting a sustained release drug delivery system including an antiviral agent in a patient in need of treatment wherein release of said agent maintains a desired concentration of said agent in blood plasma for at least 7 days.  
     
     
         76 . A method comprising: 
 forming a core including a drug;    coating the core with a polymeric skin; and    forming the core and polymeric skin into a device shaped and sized for injection.    
     
     
         77 . The method of  claim 76 , further characterized by one or more of: 
 A) the core comprises a plurality of drugs,    B) forming the core comprises extruding the core,    C) forming the core comprises compressing a mixture including the drug into the shape of the core,    D) coating the core comprises spraying the polymeric skin onto the core,    E) coating the core comprises dip coating the core into an uncured polymer,    F) coating the core comprises leaving at least one surface of the core uncoated,    G) the device is cylindrical, and    H) the method further comprises attaching an anchor to the device.    
     
     
         78 - 84 . (canceled)