# US 2024/0189239 A1 · Process for continuous hot melt granulation of low soluble pharmaceuticals > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2024/0189239 A1 - Document ID: US20240189239A1 - Status: Published application - Kind: A1 - Application number: 18/284,883 - Filed: 2022-03-31 - Published: 2024-06-13 - Earliest claimed: 2021-04-01 - Assignees: Merck Patent GmbH - Applicants: Merck Patent GmbH - Inventors: Thomas KIPPING; Finn BAUER; Nicole DI GALLO; Anja-Nadine KNUETTEL; Alessandro Giuseppe ELIA - Web page: https://patentgrep.com/patent/US20240189239A1 ## CPC - A61K 9/2027: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates} - A61K 9/146: {with organic macromolecular compounds} - A61K 9/1635: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates} - A61K 9/1682: {Processes} - A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} - A61P 17/00: Drugs for dermatological disorders - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to a process for loading a polymer with an active pharmaceutical ingredient in a melt granulation process and to the prepared product. More specifically the invention relates to a process of preparing granules which contain at least one active pharmaceutical ingredient and polyvinyl alcohol. ## Claims ### Claim 1 A process of loading a polymer with an active pharmaceutical ingredient in a melt granulation process comprising the steps of: a) kneading a mixture comprising at least one active pharmaceutical ingredient and polyvinyl alcohol in a heated screw barrel of an extruder wherein the temperature in at least one zone along the length of the screw barrel is above the melting temperature of the at least one active pharmaceutical ingredient and below the decomposition temperature of the polyvinyl alcohol to form a kneaded mixture and b) transporting the kneaded mixture through an outlet. ### Claim 2 (depends on 1) The process according to claim 1, wherein the outlet does not exert pressure on the mixture. ### Claim 3 (depends on 1) The process according to claim 1, wherein the active pharmaceutical ingredient in the granules is dispersed in an amorphous form within the polyvinyl alcohol. ### Claim 4 (depends on 1) The process according to claim 1, wherein the temperature in at least one zone along the length of the screw barrel is above the melting temperature of the at least one active pharmaceutical ingredient and below the melting temperature of the polyvinyl alcohol and wherein the kneaded mixture is transported through an outlet to obtain granules. ### Claim 5 (depends on 1) The process according to claim 1, wherein the granulation process is a twin-screw melt granulation process. ### Claim 6 (depends on 1) The process according to claim 1, wherein the polyvinyl alcohol has a hydrolysis degree of 72% to 90% and a viscosity of a 4% solution at 20° ° C. of 2 mPas to 40 mPas. ### Claim 7 (depends on 1) The process according to claim 1, wherein the polyvinyl alcohol is selected from a list consisting of PVA 3-80, PVA 3-81, PVA 3-82, PVA 3-83, PVA 3-85, PVA 3-88, PVA 3-98, PVA 4-88, PVA 4-98, PVA 5-74, PVA 5-82, PVA 6-88, PVA 6-98, PVA 8-88, PVA 10-98, PVAPVA 13-88, PVA 15-99, PVA 18-88, PVA 20-98, PVA 23-88, PVA 26-80, PVA 26-88, PVA 28-99, PVA 30-98, PVA 30-92, PVA 32-88 and PVA 40-88. ### Claim 8 (depends on 1) The process according to claim 1, wherein the polyvinyl alcohol is PVA 4-88. ### Claim 9 (depends on 1) The process according to claim 1, wherein the polyvinyl alcohol is cryo-milled. ### Claim 10 (depends on 1) The process according to claim 1, wherein the active pharmaceutical ingredient is present in the mixture in a weight ratio of active pharmaceutical ingredient to polyvinyl alcohol in the range of 1:99 to 90:10. ### Claim 11 (depends on 1) The process according to claim 1, wherein the active pharmaceutical ingredient has a poor solubility in water. ### Claim 12 (depends on 1) The process according to claim 1, wherein the granules are further milled to an average particle size between 50 μm to 300 μm. ### Claim 13 (depends on 1) The process according to claim 1, wherein the granules are further processed into tablets. ### Claim 14 (depends on 1) Granules obtainable by a process according to claim 1. ### Claim 15 (depends on 13) Tablets obtainable by a process according to claim 13. ### Claim 16 (depends on 1) The process according to claim 1, wherein the temperature in said at least one zone along the length of the screw barrel is between 40° C. to 250° C. ### Claim 17 (depends on 1) The process according to claim 1, wherein the temperature in said at least one zone along the length of the screw barrel is between 140° C. to 230° C. ### Claim 18 (depends on 1) The process according to claim 1, wherein the active pharmaceutical ingredient is present in the mixture in a weight ratio of active pharmaceutical ingredient to polyvinyl alcohol in the range of 10:90 to 30:70. ### Claim 19 (depends on 4) The process according to claim 4, wherein the granules have an average particle size between 20-2500 μm. ### Claim 20 (depends on 4) The process according to claim 4, wherein the granules comprise at least 50% (w/w) of the active pharmaceutical ingredient.