# US 10,307,421 B2 · Bromocriptine formulations > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,307,421 B2 - Document ID: US10307421B2 - Status: Granted - Kind: B2 - Application number: 15/981,752 - Filed: 2018-05-16 - Published: 2018-09-20 - Granted: 2019-06-04 - Earliest claimed: 2012-04-30 - Assignees: VeroScience LLC - Applicants: VeroScience LLC - Inventors: Anthony H. Cincotta; Craig Michael Bowe; Paul Clark Stearns; Laura Jean Weston - Web page: https://patentgrep.com/patent/US10307421B2 ## CPC - A61K 31/4985: Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems - A61K 9/14: Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)} - A61K 9/2009: {Inorganic compounds} - A61K 9/2013: {Organic compounds, e.g. phospholipids, fats} - A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates} - A61K 9/2059: {Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin} - A61K 9/2072: {characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms (A61K9/0004, A61K9/0056, A61K9/0065 take precedence)} - A61K 9/2077: {Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets} - A61K 9/2095: {Tabletting processes} - A61K 31/48: Ergoline derivatives, e.g. lysergic acid, ergotamine - A61P 3/08: for glucose homeostasis (pancreatic hormones A61P5/48) - A61P 3/10: for hyperglycaemia, e.g. antidiabetics - A61P 25/16: Anti-Parkinson drugs - 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 application describes pharmaceutical formulations of bromocriptine mesylate and methods of manufacturing and using such formulations. The formulations are useful for improving glycemic control in the treatment of type 2 diabetes. ## Claims ### Claim 1 A method for the manufacture of a dosage form, comprising: processing bromocriptine to reduce its average particle size; blending the processed bromocriptine with one or more excipients to form a mixture; and compressing the mixture to form a solid dosage form, wherein the solid dosage form provides a dissolution profile, when tested in USP Apparatus Type 2 Paddle Method at 50 rpm in 500 mL of 0.1 N hydrochloric acid at about 37° C., wherein at least about 80% of the bromocriptine has been released at about 30 minutes. ### Claim 2 (depends on 1) The method of claim 1, wherein the bromocriptine has a Dv90 of about 10 μm or lower. ### Claim 3 (depends on 1) The method of claim 1, wherein the bromocriptine has volume-based particle size distribution with a span of about 2 or lower. ### Claim 4 (depends on 1) The method of claim 1, wherein the dosage form provides a dissolution profile, when tested in USP Apparatus Type 2 Paddle Method at 50 rpm in 500 mL of 0.1 N hydrochloric acid at about 37° C., wherein at least about 90% of the bromocriptine has been released at about 30 minutes. ### Claim 5 (depends on 1) The method of claim 1, wherein the dosage form provides a dissolution profile, when tested in USP Apparatus Type 2 Paddle Method at 50 rpm in 500 mL of 0.1 N hydrochloric acid at about 37° C., wherein not more than about 50% of the bromocriptine has been released at about 7 minutes, and not more than about 75% of the bromocriptine has been released at about 10 minutes. ### Claim 6 (depends on 1) The method of claim 1, wherein the wherein the dosage form exhibits a pharmacokinetic profile wherein the time to maximum plasma concentration (Tmax) of bromocriptine is between about 30 and about 60 minutes following oral administration of the dosage form to a subject under fasting conditions or the Tmax of bromocriptine is between about 90 and about 120 minutes following oral administration of the dosage form to the subject under high fat fed conditions. ### Claim 7 A method for the manufacture of a dosage form, comprising: processing bromocriptine to reduce its average particle size and provide bromocriptine in micronized form; blending the bromocriptine with one or more excipients to form a mixture; and compressing the mixture to form a solid dosage form, wherein the dosage form provides a dissolution profile, when tested in USP Apparatus Type 2 Paddle Method at 50 rpm in 500 mL of 0.1 N hydrochloric acid at about 37° C., wherein at least about 80% of the bromocriptine has been released at about 30 minutes. ### Claim 8 (depends on 7) The method of claim 7, wherein the bromocriptine has a Dv90 of about 20 μm or lower. ### Claim 9 (depends on 7) The method of claim 7, wherein the bromocriptine has volume-based particle size distribution with a span of about 2 or lower. ### Claim 10 (depends on 7) The method of claim 7, wherein the dosage form provides a dissolution profile, when tested in USP Apparatus Type 2 Paddle Method at 50 rpm in 500 mL of 0.1 N hydrochloric acid at about 37° C., wherein at least about 90% of the bromocriptine has been released at about 30 minutes. ### Claim 11 (depends on 7) The method of claim 7, wherein the dosage form provides a dissolution profile, when tested in USP Apparatus Type 2 Paddle Method at 50 rpm in 500 mL of 0.1 N hydrochloric acid at about 37° C., wherein not more than about 50% of the bromocriptine has been released at about 7 minutes, and not more than about 75% of the bromocriptine has been released at about 10 minutes. ### Claim 12 (depends on 7) The method of claim 7, wherein the dosage form exhibits a pharmacokinetic profile wherein the time to maximum plasma concentration (Tmax) of bromocriptine is between about 30 and about 60 minutes following oral administration of the dosage form to the subject under fasting conditions or the Tmax of bromocriptine is between about 90 and about 120 minutes following oral administration of the dosage form to a subject under high fat fed conditions. ### Claim 13 (depends on 7) The method of claim 7, wherein the bromocriptine has a Dv90 of about 15 μm or lower; and wherein the bromocriptine has a particle size distribution with a span of about 2 or lower. ### Claim 14 (depends on 13) The method of claim 13, wherein the dosage form provides a dissolution profile, when tested in USP Apparatus Type 2 Paddle Method at 50 rpm in 500 mL of 0.1 N hydrochloric acid at about 37° C., wherein at least about 90% of the bromocriptine has been released at about 30 minutes. ### Claim 15 (depends on 13) The method of claim 13, wherein the dosage form provides a dissolution profile, when tested in USP Apparatus Type 2 Paddle Method at 50 rpm in 500 mL of 0.1 N hydrochloric acid at about 37° C., wherein not more than about 50% of the bromocriptine has been released at about 7 minutes, and not more than about 75% of the bromocriptine has been released at about 10 minutes. ### Claim 16 (depends on 13) The method of claim 13, wherein the wherein the dosage form exhibits a pharmacokinetic profile wherein the time to maximum plasma concentration (Tmax) of bromocriptine is between about 30 and about 60 minutes following oral administration of the dosage form to a subject under fasting conditions or the Tmax of bromocriptine is between about 90 and about 120 minutes following oral administration of the dosage form to the subject under high fat fed conditions. ### Claim 17 (depends on 1) The method of claim 1 wherein the bromocriptine has a Dv99 of less than about 15 μm; and wherein the dosage form has a dissolution profile wherein at least about 80% of the bromocriptine has been released at about 30 minutes, when tested in USP Apparatus Type 2 Paddle Method at 50 rpm in 500 mL of 0.1 N hydrochloric acid at about 37° C. ### Claim 18 (depends on 17) The method of claim 17, comprising determining that the bromocriptine has a Dv99 of about 15 μm or lower. ### Claim 19 (depends on 17) The method of claim 17, wherein the dosage form provides a dissolution profile, when tested in USP Apparatus Type 2 Paddle Method at 50 rpm in 500 mL of 0.1 N hydrochloric acid at about 37° C., wherein at least about 90% of the bromocriptine has been released at about 30 minutes. ### Claim 20 (depends on 17) The method of claim 17, wherein the dosage form provides a dissolution profile, when tested in USP Apparatus Type 2 Paddle Method at 50 rpm in 500 mL of 0.1 N hydrochloric acid at about 37° C., wherein not more than about 50% of the bromocriptine has been released at about 7 minutes, and not more than about 75% of the bromocriptine has been released at about 10 minutes. ### Claim 21 (depends on 17) The method of claim 17, wherein the wherein the dosage form exhibits a pharmacokinetic profile wherein the time to maximum plasma concentration (Tmax) of bromocriptine is between about 30 and about 60 minutes following oral administration of the dosage form to a subject under fasting conditions or the Tmax of bromocriptine is between about 90 and about 120 minutes following oral administration of the dosage form to the subject under high fat fed conditions. ### Claim 22 (depends on 1) The method of claim 1 wherein the bromocriptine has a Dv50 of 5 μm or lower and a span of 2 or lower; and wherein the dosage form provides a dissolution profile, when tested in USP Apparatus Type 2 Paddle Method at 50 rpm in 500 mL of 0.1 N hydrochloric acid at about 37° C., wherein at least about 80% of the bromocriptine has been released at about 30 minutes. ### Claim 23 (depends on 22) The method of claim 22, wherein the dosage form provides a dissolution profile, when tested in USP Apparatus Type 2 Paddle Method at 50 rpm in 500 mL of 0.1 N hydrochloric acid at about 37° C., wherein at least about 90% of the bromocriptine has been released at about 30 minutes. ### Claim 24 (depends on 22) The method of claim 22, wherein the dosage form provides a dissolution profile, when tested in USP Apparatus Type 2 Paddle Method at 50 rpm in 500 mL of 0.1 N hydrochloric acid at about 37° C., wherein not more than about 50% of the bromocriptine has been released at about 7 minutes, and not more than about 75% of the bromocriptine has been released at about 10 minutes. ### Claim 25 (depends on 22) The method of claim 22, wherein the wherein the dosage form exhibits a pharmacokinetic profile wherein the time to maximum plasma concentration (Tmax) of bromocriptine is between about 30 and about 60 minutes following oral administration of the dosage form to a subject under fasting conditions or the Tmax of bromocriptine is between about 90 and about 120 minutes following oral administration of the dosage form to the subject under high fat fed conditions.