# US 2023/0057790 A1 · Injectable controlled-release formulations of progestogen drugs > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2023/0057790 A1 - Document ID: US20230057790A1 - Status: Published application - Kind: A1 - Application number: 17/791,977 - Filed: 2021-02-15 - Published: 2023-02-23 - Earliest claimed: 2020-02-26 - Assignees: FORDOZ Pharma Corp. - Applicants: FORDOZ Pharma Corp. - Inventors: Sydney Ugwu; Zengli Fu; James He - Web page: https://patentgrep.com/patent/US20230057790A1 ## CPC - A61K 9/1647: {Polyesters, e.g. poly(lactide-co-glycolide)} - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 31/57: substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone - A61P 15/02: for disorders of the vagina - A61P 15/08: for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis - A61P 15/18: Feminine contraceptives - 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 injectable microspheres and formulations comprising the microspheres for controlled release of progestogen hormones. ## Claims ### Claim 1 An injectable sustained-release formulation, comprising: (a) microspheres comprising a progestogen compound and a biodegradable composition comprising one or more poly(lactic-co-glycolic acid) copolymers (PLGA), wherein the progestogen compound can be released in a sustained and controlled manner with a linear or substantially linear cumulative release profile up to at least about 70% of accumulated release within a controlled time period and substantially without an initial burst or a lag phase; and (b) a diluent solution in which the microspheres are suspended wherein the PLGA polymer has a molar ratio of lactide to glycolide between about 90:10 and about 40:60 and a molecular weight in the range between 4 kD and 120 kD; wherein the progestogen compound is present in an amount of between about 10% and about 50% by weight of the microspheres; and the microspheres encapsulating the progestogen compound have a mean diameter of between about 20 μm and about 150 μm. ### Claim 2 (depends on 1) The formulation of claim 1, wherein the progestogen compound is selected from the group consisting of natural progestogen compounds, synthetic progestogen compounds, and combinations of synthetic progestogen and estrogens. ### Claim 3 (depends on 2) The formulation of claim 2, wherein the natural progestogen is progesterone. ### Claim 4 (depends on 2) The formulation of claim 2, wherein the synthetic progestogen is selected from the group consisting of medroxyprogesterone acetate, hydroxyprogesterone caproate, northindrone, northindrone acetate, ethynodiol diacetate, desogestrel, norgestrel, levonorgestrel, norgestimate, gestodene, and drospirenone. ### Claim 5 (depends on 2) The formulation of claim 2, wherein the synthetic progestogen is combined with an estrogen. ### Claim 6 (depends on 1) The formulation of claim 1, wherein the PLGA polymer has a molar ratio of lactide to glycolide between about 50:50 and about 75:25. ### Claim 7 (depends on 1) The formulation of claim 1, wherein the PLGA polymer chains are carboxyl-terminated or ester-terminated. ### Claim 8 (depends on 1) The formulation of claim 1, wherein the PLGA polymer has a molecular weight in the range between 4 kD and 75 kD. ### Claim 9 (depends on 1) The formulation of claim 1, wherein microspheres comprise a mixture of the PLGA polymers having different lactide to glycolide ratios, and/or different average molecular weights, and/or different chain-end groups. ### Claim 10 (depends on 9) The formulation of claim 9, wherein the mixture of PLGA polymers comprises at least one carboxyl-terminated PLGA polymer with a molecular weight of about 5 kD to about 40 kD. ### Claim 11 (depends on 1) The formulation of claim 1, wherein the progestogen compound is in an amount of between about 20% and about 50% by weight of the microspheres. ### Claim 12 (depends on 11) The formulation of claim 11, wherein the progestogen compound is progesterone in an amount of between about 35% and about 45% by weight of the microspheres. ### Claim 13 (depends on 1) The formulation of claim 1, having a linear cumulative release profile up to at least about 80% of accumulated release of progesterone and substantially without any initial burst or lag phase, and the total time of the linear-stage release is about 6 to 8 days. ### Claim 14 (canceled) ### Claim 15 (depends on 1) A method of making an injectable sustained-release formulation according to claim 1, comprising: 1) preparing an organic dispersed phase comprising one or more PLGA copolymers, an organic solvent or a mixture of organic solvents, and a progestogen compound; 2) mixing the organic dispersed phase with an aqueous continuous phase comprising water and polyvinyl alcohol (PVA) to form an oil-in-water (O/W) emulsion; 3) removing the organic solvent(s) in the O/W emulsion by extraction and/or evaporation to form solid drug-loaded PLGA microspheres; 4) drying the drug-loaded microspheres; and 5) suspending the dried drug-loaded microspheres in a diluent solution, wherein the diluent solution comprises a surface active wetting agent, a viscosity enhancing agent, a tonicity agent, a pH buffering agent, and water for injection. ### Claim 16 (depends on 15) The method of claim 15, wherein the organic solvent is dichloromethane or a mixture of dichloromethane and other organic solvent(s). ### Claim 17 (depends on 15) The method of claim 15, wherein the progestogen compound is progesterone. ### Claim 18 (depends on 17) The method of claim 17, wherein the injectable sustained-release formulation of progesterone has a linear cumulative release profile up to at least about 80% of accumulated release and substantially without any initial burst or lag phase, and the total time of the linear-stage release is about 6 to 8 days. ### Claim 19 (canceled) ### Claim 20 (depends on 15) The method of claim 15, wherein the diluent solution comprises polysorbate 20, carboxymethyl cellulose sodium, sodium chloride, citric acid, and di-sodium hydrogen phosphate. ### Claim 21 (depends on 1) A method of preventing pregnancy and treating gynecological disorders or providing treatment to support pregnancy and fertility in women, comprising locally injecting to a subject in need thereof a therapeutically effective amount of the injectable sustained-release formulation of claim 1. ### Claim 22 (depends on 21) The method of claim 21, wherein the gynecological disorder is selected from the group consisting of secondary amenorrhea, endometriosis, abnormal uterine bleeding due to hormonal imbalance, and acne.