# US 2024/0197635 A1 · Dissociating polymer matrix compositions of fulvestrant and methods of their making and use > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2024/0197635 A1 - Document ID: US20240197635A1 - Status: Published application - Kind: A1 - Application number: 18/548,816 - Filed: 2022-03-03 - Published: 2024-06-20 - Earliest claimed: 2021-03-03 - Assignees: VeraMorph LLC - Applicants: VeraMorph LLC - Inventors: Paul Douglas Godfrin - Web page: https://patentgrep.com/patent/US20240197635A1 ## CPC - A61K 9/146: {with organic macromolecular compounds} - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 31/565: not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol - A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} - 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 the composition and methods of manufacturing and use of dissociating polymeric matrix oral dosages (disintegrating pre-formed oral dosage hydrogels) loaded with fulvestrant as an orally delivered therapy for the treatment of diseases, particularly cancer and especially metastatic breast cancer. ## Claims ### Claim 1 A composition comprising: a dissociating polymer matrix comprising single- or multi-component polymer chains connected by one or more hydrolytically degradable cross-linkers covalently linked to said polymer chains defining pores within the polymer matrix and fulvestrant encapsulated within the pores of the dissociating polymer matrix. ### Claim 2 (depends on 1) The composition of claim 1, wherein the one or more hydrolytically degradable cross-linkers comprise one or more hydrolytically degradable group selected from acetal, anhydride, boronic ester, carbonate, ketal, or silyl ether groups. ### Claim 3 (depends on 1) The composition of claim 1, wherein the one or more hydrolytically degradable cross-linkers comprise a central poly(ethylene glycol) segment of molecular weight no less than about 150 g/mol with both terminal hydroxyl groups attached to a ketal or acetal functional group with a PEG methacrylate with a molecular weight no less than about 174 g/mol. ### Claim 4 (depends on 1) The composition of claim 1, wherein the dissociating polymer matrix comprises between about 10% to 90% by mole of the one or more hydrolytically degradable cross-linkers and between about 10% to 90% by mole of additional monomers selected from the group consisting of methyl methacrylate and butyl methacrylate. ### Claim 5 (canceled) ### Claim 6 (depends on 4) The composition of claim 4, wherein the polymer chains connected by the one or more hydrolytically degradable cross-linkers comprises butyl methacrylate at a molar percentage of 25% to 75%. ### Claim 7 (depends on 4) The composition of claim 4, wherein the polymer chains connected by the one or more hydrolytically degradable cross-linkers comprises butyl methacrylate at a molar percentage of 40% to 60%. ### Claim 8 (depends on 1) The composition of claim 1, wherein the fulvestrant is in a solid state. ### Claim 9 (depends on 8) The composition of claim 8, wherein the solid state is selected from an amorphous state or a nanocrystalline state. ### Claim 10 (depends on 9) The composition of claim 9, wherein the solid state is the nanocrystalline state comprising an average crystal size of between 10 nm and 1000 nm. ### Claim 11 (depends on 1) The composition of claim 1, wherein the fulvestrant comprises between 5% and 80% by weight of the combined mass of the dissociating polymer matrix and encapsulated fulvestrant. ### Claim 12 (depends on 1) The composition of claim 1, wherein the fulvestrant comprises between 5% and 50% by weight of the combined mass of the dissociating polymer matrix and encapsulated fulvestrant. ### Claim 13 (canceled) ### Claim 14 (canceled) ### Claim 15 (depends on 1) The composition of claim 1, wherein the composition has a shelf-life in which chemical integrity of fulvestrant is maintained for at least 28 days under accelerated storage conditions. ### Claim 16 (depends on 1) An oral pharmaceutical dosage unit comprising the composition of claim 1, wherein the fulvestrant is present in a therapeutically effective amount. ### Claim 17 (depends on 16) The oral pharmaceutical dosage unit of claim 16, wherein the dosage unit is in a solid form. ### Claim 18 (depends on 16) The oral pharmaceutical dosage unit of claim 16, wherein the dosage unit is a tablet, a mini tablet, a film coated tablet, or a capsule comprising a hard outer shell containing a powder and/or mini tablets. ### Claim 19 (depends on 16) The oral pharmaceutical dosage unit of claim 16, wherein the oral pharmaceutical dosage unit contains between 20 mg and 1000 mg of fulvestrant. ### Claim 20 (canceled) ### Claim 21 (canceled) ### Claim 22 (depends on 16) The oral pharmaceutical dosage unit of claim 16, wherein the hydrolytically degradable cross-linkers degrade under acidic and/or neutral conditions ranging in pH from 0-7. ### Claim 23 (depends on 16) The oral pharmaceutical dosage unit of claim 16, wherein the hydrolytically degradable cross-linkers degrade within about 10 to 60 minutes. ### Claim 24 (depends on 1) A method of manufacturing a composition of claim 1, said method comprising: creating a first solution comprising between about 10% to 30% by volume hydrolytically degradable cross-linker, between about 2% to 6% by volume butyl methacrylate, and an effective amount of an initiator; exposing the first solution to an initiation source to polymerize the butyl methacrylate and cross-linker to form a dissociating polymer matrix; combining the dissociating polymer matrix with a second solution comprising fulvestrant at a concentration of between 10 mg/mL to 500 mg/mL to form a dissociating polymer matrix/fulvestrant mixture; and drying the dissociating polymer matrix/fulvestrant mixture until the fulvestrant is solidified in pores of the dissociating polymer matrix to form the dissociating polymer matrix which encapsulates fulvestrant. ### Claim at position 25 -29. (canceled) ### Claim 30 (depends on 1) A method of treating metastatic breast cancer in a subject, said method comprising: administering to a subject in need thereof a therapeutically effective amount of the composition of claim 1 or an oral dosage unit comprising same. ### Claim 31 (canceled) ### Claim 32 (canceled)