Drug delivery devices comprising biodegradable protein for the controlled release of pharmacologically active agents and method of making the drug delivery devices

Abstract

The present invention relates to an improved method of making drug delivery devices for the controlled release of pharmacologically active agents and further, to drug delivery devices made by such method. More specifically, the present invention relates to a method of forming a film comprising one or more biodegradable polymeric materials, one or more pharmacologically active agents, and one or more biocompatible solvents. The film is then partially dried, rolled or otherwise shaped, and then compressed. In this manner, the amount of pharmacologically active agent(s) that can be incorporated into the drug delivery device is increased and the pharmacologically active agent(s) is/are substantially homogeneously distributed throughout the drug delivery device. As a result, the release characteristics of the pharmacologically active agent from the drug delivery device are enhanced.

What is claimed is:  
     
         1 . A method of making a drug delivery device, comprising the steps of: 
 (a) preparing a coatable composition comprising one or more biodegradable polymeric materials, one or more pharmacologically active agents, and one or more biocompatible solvents;    (b) coating the composition to form a film;    (c) drying the coated film until the coated film can be formed into a cohesive body;    (d) forming said cohesive body; and    (e) compressing the cohesive body to form a drug delivery device.    
     
     
         2 . The method of  claim 1 , wherein the biodegradable polymeric material comprises a biodegradable protein.  
     
     
         3 . The method of  claim 2 , wherein the biodegradable protein comprises a naturally occurring protein.  
     
     
         4 . The method of  claim 3 , wherein the naturally occurring protein comprises elastin.  
     
     
         5 . The method of  claim 2 , wherein the biodegradable protein comprises a genetically engineered protein.  
     
     
         6 . The method of  claim 5 , wherein the genetically engineered protein comprises silk-like blocks and elastin-like blocks.  
     
     
         7 . The method of  claim 3 , wherein the drug delivery device further comprises an additive to enhance the release characteristics of the pharmacologically active agent.  
     
     
         8 . The method of  claim 7 , wherein the additive comprises one or more fatty acid monomers.  
     
     
         9 . The method of  claim 8 , wherein the fatty acid monomers comprise a erucic dimer and sebacic acid.  
     
     
         10 . The method of  claim 9 , wherein the ratio of fatty acid dimer to sebacic acid is 1:4 based upon weight.  
     
     
         11 . The method of  claim 10 , wherein the biodegradable polymeric material comprises a genetically engineered protein comprising silk-like blocks and elastin-like blocks and wherein the ratio of the genetically engineered protein to the fatty acid dimer:sebacic acid copolymer is about 2:1, based upon weight.  
     
     
         12 . The method of  claim 1 , wherein the cohesive body is compressed at a pressure of from about 100 psi to about 30,000 psi for a time period of from about 10 seconds to about 48 hours.  
     
     
         13 . The method of  claim 12 , wherein the cohesive body is compressed at a pressure of from about 1000 psi to about 4000 psi for a time period of from about 1 minute to about 60 minutes.  
     
     
         14 . The method of  claim 1 , wherein the cohesive body is compressed into the form of a cylinder.  
     
     
         15 . The method of  claim 14 , wherein the cylinder is subsequently cut into discs.  
     
     
         16 . The method of  claim 1 , wherein the pharmacologically active agent comprises a corticosteroid.  
     
     
         17 . The method of  claim 16 , wherein the pharmacologically active agent comprises dexamethasone.  
     
     
         18 . The method of  claim 1 , wherein the pharmacologically active agent comprises a neurotoxin.  
     
     
         19 . The method of  claim 20 , wherein the neurotoxin is capsaicin.  
     
     
         20 . The method of  claim 1 , wherein the pharmacologically active agent comprises an opioid analgesic.  
     
     
         21 . The method of  claim 20 , wherein opioid analgesic comprises sulfentanil.  
     
     
         22 . The method of  claim 1 , wherein the pharmacologically active agent is a local anesthetic.  
     
     
         23 . The method of  claim 22 , wherein the local anesthetic comprises bupivacaine, lidocaine, or a combination thereof.  
     
     
         24 . The method of  claim 1 , wherein the pharmacologically active agent comprises an enzyme.  
     
     
         25 . The method of  claim 24 , wherein the coatable composition further comprises an amount of an enzyme substrate.  
     
     
         26 . The method of  claim 1 , wherein the pharmacologically active agent comprises a second, migration-vulnerable drug delivery device.  
     
     
         27 . The method of  claim 26 , wherein the migration-vulnerable drug delivery device comprises a plurality of lipospheres homogeneously dispersed within the drug delivery device.  
     
     
         28 . The method of  claim 27 , wherein the migration-vulnerable drug delivery device comprises a plurality of microspheres homogeneously dispersed within the drug delivery device.  
     
     
         29 . The method of  claim 1 , wherein the pharmacologically active agent is substantially homogeneously distributed within the drug delivery device.  
     
     
         30 . The method of  claim 1 , wherein the biodegradable polymeric material comprises at least one polymeric material that degrades quickly and at least one polymeric material that degrades slowly relative to one another.  
     
     
         31 . A drug delivery device comprising a compressed matrix comprising at least one biodegradable polymeric material and a plurality of lipospheres comprising an encapsulated pharmacologically active agent, wherein said plurality of lipospheres is substantially homogeneously distributed within the matrix.  
     
     
         32 . A drug delivery device comprising a compressed matrix comprising at least one biodegradable polymeric material and a plurality of microspheres comprising an encapsulated pharmacologically active agent, wherein said plurality of microspheres is substantially homogeneously distributed within the matrix.  
     
     
         33 . A drug delivery device comprising a compressed matrix comprising at least one biodegradable protein and a macromolecular pharmacologically active agent, wherein said macromolecular pharmacologically active agent is substantially homogeneously distributed within the matrix.  
     
     
         34 . A method of erecting a local therapeutic response in a patient in need of such treatment comprising the step of delivering a drug delivery device to the site at which a local therapeutic response is desired, wherein said drug delivery device comprises a compressed matrix comprising at least one biodegradable polymeric material, at least one pharmacologically active agent, and at least one biocompatible solvent, wherein said pharmacologically active agent is substantially homogeneously distributed within the matrix.  
     
     
         35 . The method of  claim 35 , wherein the therapeutic response effected is an analgesic response.  
     
     
         36 . The method of  claim 35 , wherein the therapeutic response effected is an anti-inflammatory response.  
     
     
         37 . The method of  claim 35 , wherein the at least one biodegradable polymeric component comprises a biodegradable protein.  
     
     
         38 . The method of  claim 36 , wherein the biodegradable protein comprises a genetically engineered protein comprising silk-like blocks and elastin-like blocks  
     
     
         39 . The method of  claim 35 , wherein the drug delivery device further comprises an additive to enhance the release characteristics of the pharmacologically active agent.  
     
     
         40 . The method of  claim 38 , wherein the additive comprises one or more fatty acid monomers.  
     
     
         41 . The method of  claim 39 , wherein the fatty acid monomers comprise a erucic acid dimer and sebacic acid.