# US 9,040,080 B2 · Processing of heat-sensitive active agents > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,040,080 B2 - Document ID: US9040080B2 - Status: Granted - Kind: B2 - Application number: 12/255,447 - Filed: 2008-10-21 - Published: 2010-04-22 - Granted: 2015-05-26 - Earliest claimed: 2008-10-21 - Assignees: Southwest Research Institute - Applicants: Hong Dixon; Joseph A McDonough - Inventors: Hong Dixon; Joseph A McDonough - Web page: https://patentgrep.com/patent/US9040080B2 ## CPC - A61J 3/07: into the form of capsules or similar small containers for oral use - A61K 9/1647: {Polyesters, e.g. poly(lactide-co-glycolide)} - A61K 9/70: Web, sheet or filament bases {; Films; Fibres of the matrix type containing drug (hollow drug-filled fibres A61K9/0092)} - A61J: CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract The present disclosure relates to a method of melt processing an active agent. The method may include encapsulating an active agent in a first polymer material exhibiting a first processing temperature T1 and forming capsules including the active agent. The method may also include melt processing the capsules with a second polymer material exhibiting a second processing temperature T2, wherein T1>T2. ## Claims ### Claim 1 A method of melt processing an active agent comprising: forming a first mixture of an active agent, a first polymer material and a first solvent S1, wherein said first solvent comprises an organic solvent and said first polymer is present in said first solvent at 1% to 20% by volume and said active agent is a nanoparticulate having a largest linear dimension of less than or equal to 500 nanometers and a degradation temperature of less than 200° C.; adding said first mixture to a second solvent and forming a second mixture including a dispersed phase of said first mixture in said second solvent, wherein said second solvent comprises a hydrocarbon; removing said first solvent from said second mixture; encapsulating said active agent in said first polymer material exhibiting a first processing temperature T1, wherein said active agent forms domains within a matrix of said first polymer, wherein said domains are discrete, and forming a plurality of capsules including said active agent; and melt processing said capsules with a second polymer material by injection molding, blow molding, extrusion, twin screw extrusion, compression molding, or transfer molding, wherein said second polymer exhibits a second processing temperature T2, wherein T1>T2, wherein said plurality of capsules are dispersed within a matrix of said second polymer and wherein said encapsulating of said active agent in the first polymer is conducted at a relatively lower temperature than said melt processing with said second polymer; and wherein said first polymer exhibits a processing temperature T1 in the range of 120° C. to 400° C., and said second polymer exhibits a processing temperature T2 in the range of less than 200° C. ### Claim 2 (depends on 1) The method of claim 1, wherein said active agent exhibits less than 2% by weight degradation after melt processing. ### Claim 3 (depends on 1) The method of claim 1, wherein said first solvent S1 and second solvent S2 have Hildebrand solubility parameter values, and said solubility parameter values have a difference that is greater than 2.0 units of one another as measured in (MPa)1/2. ### Claim 4 (depends on 1) The method of claim 1, wherein said active agent is a carbonic anhydrase inhibitor. ### Claim 5 (depends on 4) The method of claim 4 wherein said carbonic anhydrase inhibitor comprises brinzolamide. ### Claim 6 (depends on 1) The method of claim 1 wherein said active agent comprises a pharmaceutical active agent. ### Claim 7 (depends on 1) The method of claim 1 wherein said active agent is selected from the group consisting of osteoporetics, estrogen uptake inhibitors, hypolipodemic agents, hormones, protoglandins and derivatives, anti-psychotic drugs and anti-inflammatories. ### Claim 8 (depends on 1) The method of claim 1, wherein said first polymer exhibits a processing temperature T1 in the range of 120° C. to 400° C., and said second polymer exhibits a processing temperature T2 in the range of less than 200° C. ### Claim 9 (depends on 1) The method of claim 1, wherein said active agent is present in said capsules in the range of 10% to 60% by weight. ### Claim 10 (depends on 1) The method of claim 1, wherein said capsules have an average diameter in the range of 0.01 μm to 100 μm, including all values and increments therein. ### Claim 11 (depends on 1) The method of claim 1, wherein said active agent exhibits a degradation temperature T3 of less than 200° C. and T1>T3. ### Claim 12 (depends on 1) The method of claim 1 wherein said melt processing of said capsules with a second polymer comprises forming fibers, films, rods, or pellets. ### Claim 13 (depends on 1) The method of claim 1 wherein said active agent comprises a food ingredient. ### Claim 14 (depends on 1) The method of claim 1 wherein said first polymer comprises a biodegradable polymer. ### Claim 15 (depends on 1) The method of claim 1 wherein said first polymer comprises a biocompatible polymer. ### Claim 16 (depends on 1) The method of claim 1 wherein said first polymer is selected from poly(lactic acid) and its copolymers, polycarbonates, poly(orthoesters), polyamides, poly(esteramides), polyurethanes, polyanhydrides, polyphosphazenes, polyhydroxyalkanoate, starch-based polymers or chitosan.