# US 11,110,084 B2 · Opioid formulations > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,110,084 B2 - Document ID: US11110084B2 - Status: Granted - Kind: B2 - Application number: 17/142,673 - Filed: 2021-01-06 - Published: 2021-05-13 - Granted: 2021-09-07 - Earliest claimed: 2012-07-26 - Assignees: Camurus AB - Applicants: Camurus AB - Inventors: Fredrik Tiberg; Ian Harwigsson; Markus Johnsson - Web page: https://patentgrep.com/patent/US11110084B2 ## CPC - A61K 31/4748: forming part of bridged ring systems (strychnine A61K31/475; morphinan derivatives A61K31/485) - A61K 9/0024: {Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L)} - A61K 31/485: Morphinan derivatives, e.g. morphine, codeine - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters - A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids - A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) - A61P 25/36: Opioid-abuse - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - 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 A depot precursor formulation comprising: a) a controlled-release matrix; b) at least oxygen containing organic solvent; c) at least 12% by weigh of at least one active agent selected from buprenorphine and salts thereof, calculated as buprenorphine free base. Corresponding depot compositions and methods of treatment in pain management, by opioid maintenance and related methods are provided. ## Claims ### Claim 1 A depot precursor formulation comprising: a) a lipid controlled release formulation comprising i) phosphatidylcholine and ii) glycerol dioleate, wherein the phosphatidylcholine is about 10 to about 25% by weight of the total weight of the depot precursor formulation, and the glycerol dioleate is about 15 to about 25% by weight of the total weight of the depot precursor formulation; b) about 25 to about 32% by weight of N-methyl-2-pyrrolidone; and c) about 25 to about 50% by weight of buprenorphine. ### Claim 2 (depends on 1) The depot precursor formulation of claim 1, wherein the depot precursor formulation is contained in a pre-filled syringe. ### Claim 3 (depends on 2) The depot precursor formulation of claim 2, wherein the depot precursor formulation within the pre-filled syringe comprises 40 to 140 mg of buprenorphine (calculated as a free base). ### Claim 4 (depends on 1) The depot precursor formulation of claim 1, wherein the depot precursor formulation has a viscosity that is about 1 to about 1000 mPas at 20° C. as measured with a CarriMed CSL 100 rheometer equipped with automatic gap setting. ### Claim 5 (depends on 1) The depot precursor formulation of claim 1, characterized in that the depot precursor formulation, when administered to a patient, exhibits a variation between Cmin and Cmax of buprenorphine at steady-state administration that is between 0.4 ng/mL and 10 ng/mL. ### Claim 6 (depends on 1) The depot precursor formulation of claim 1, wherein the depot precursor formulation, after contact with an aqueous fluid, forms a liquid crystalline phase structure. ### Claim 7 (depends on 6) The depot precursor formulation of claim 6, wherein the liquid crystalline phase structure is a non-lamellar crystalline phase structure. ### Claim 8 (depends on 1) The depot precursor formulation of claim 1, wherein the depot precursor formulation comprises: about 35% by weight of buprenorphine; about 14% by weight of a phosphatidylcholine; about 21% by weight of glycerol dioleate; and about 30% by weight of N-methyl-2-pyrrolidone. ### Claim 9 (depends on 1) The depot precursor formulation of claim 1, wherein the depot precursor formulation comprises: about 35% by weight of buprenorphine; about 17.5% by weight of a phosphatidylcholine; about 17.5% by weight of glycerol dioleate; and about 30% by weight of N-methyl-2-pyrrolidone. ### Claim 10 (depends on 1) The depot precursor formulation of claim 1, wherein the depot precursor formulation comprises: about 30% by weight of buprenorphine; about 25% by weight of a phosphatidylcholine; about 25% by weight of glycerol dioleate; and about 20% by weight of N-methyl-2-pyrrolidone. ### Claim 11 (depends on 1) The depot precursor formulation of claim 1, wherein the depot precursor formulation comprises: about 30% by weight of buprenorphine; about 16% by weight of a phosphatidylcholine; about 24% by weight of glycerol dioleate; and about 30% by weight of N-methyl-2-pyrrolidone. ### Claim 12 A method of administering an opioid maintenance treatment to a subject, the method comprising administering a depot precursor formulation once monthly to the subject, wherein the depot precursor formulation comprises: a) a lipid controlled release formulation comprising i) phosphatidylcholine and ii) glycerol dioleate, wherein the phosphatidylcholine is about 10 to about 25% by weight of the total weight of the depot precursor formulation, and the glycerol dioleate is about 15 to about 25% by weight of the total weight of the depot precursor formulation; b) about 25 to about 32% by weight of N-methyl-2-pyrrolidone; and c) about 25 to about 50% by weight of buprenorphine. ### Claim 13 (depends on 12) The method of claim 12, wherein the depot precursor formulation is administered from a pre-filled syringe. ### Claim 14 (depends on 13) The method of claim 13, wherein the pre-filled syringe contains less than 1 mL of the depot precursor formulation. ### Claim 15 (depends on 14) The method of claim 14, wherein the depot precursor formulation comprises 40 to 140 mg of buprenorphine (calculated as a free base). ### Claim 16 (depends on 13) The method of claim 13, wherein the pre-filled syringe comprises a needle having a gauge greater than 18 G. ### Claim 17 (depends on 13) The method of claim 13, wherein the pre-filled syringe further comprises a needle stick prevention safety device. ### Claim 18 (depends on 13) The method of claim 13, wherein the pre-filled syringe is disposable. ### Claim 19 (depends on 12) The method of claim 12, wherein the depot precursor formulation provides a variation between Cmin and Cmax of buprenorphine at steady-state administration that is between 0.4 ng/mL and 10 ng/mL. ### Claim 20 (depends on 12) The method of claim 12, wherein the patient suffers from an opioid dependency. ### Claim 21 (depends on 12) The method of claim 12, wherein the patient suffers from opioid withdrawal. ### Claim 22 (depends on 12) The method of claim 12, wherein administering the opioid maintenance treatment treats pain in the patient. ### Claim 23 (depends on 12) The method of claim 12, wherein the patient is receiving or has previously received an oral dosage form comprising buprenorphine. ### Claim 24 (depends on 13) The method of claim 13, wherein the oral dosage form is sublingual. ### Claim 25 (depends on 12) The method of claim 12, wherein the depot precursor formulation, after contact with an aqueous fluid, forms a liquid crystalline phase structure. ### Claim 26 (depends on 15) The method of claim 15, wherein the liquid crystalline phase structure is a non-lamellar crystalline phase structure. ### Claim 27 (depends on 12) The method of claim 12, wherein the depot precursor formulation comprises: about 35% by weight of buprenorphine; about 14% by weight of a phosphatidylcholine; about 21% by weight of glycerol dioleate; and about 30% by weight of N-methyl-2-pyrrolidone. ### Claim 28 (depends on 12) The method of claim 12, wherein the depot precursor formulation comprises: about 35% by weight of buprenorphine; about 17.5% by weight of a phosphatidylcholine; about 17.5% by weight of glycerol dioleate; and about 30% by weight of N-methyl-2-pyrrolidone. ### Claim 29 (depends on 12) The method of claim 12, wherein the depot precursor formulation comprises: about 30% by weight of buprenorphine; about 25% by weight of a phosphatidylcholine; about 25% by weight of glycerol dioleate; and about 20% by weight of N-methyl-2-pyrrolidone. ### Claim 30 (depends on 12) The method of claim 12, wherein the depot precursor formulation comprises: about 30% by weight of buprenorphine; about 16% by weight of a phosphatidylcholine; about 24% by weight of glycerol dioleate; and about 30% by weight of N-methyl-2-pyrrolidone.