Bromocriptine formulations
Inventors
Cincotta, Anthony H. • Bowe, Craig Michael • Stearns, Paul Clark • Weston, Laura Jean
Assignees
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Publication Number
US-11666567-B2
Publication Date
2023-06-06
Expiration Date
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.
Core Innovation
The invention relates to bromocriptine and one or more excipients in an oral dosage form that provides for absorption of a substantial amount of bromocriptine through the gastric and/or intestinal mucosa when administered to a subject. The bromocriptine is defined by particle size metrics, including DV90 less than 15 bcm and Dv10 of less than 2 bcm, or alternatively Dv90 about 15 bcm or lower, Dv50 about 8 bcm or lower, and Dv10 about 3 bcm or lower.
The dosage form exhibits a pharmacokinetic profile where Tmax is between about 30 and about 60 minutes following oral administration under fasting conditions, and between about 90 and about 120 minutes following oral administration under high fat fed conditions. The particle size distribution is used as a key determinant, including volume-based particle size distribution parameters and span, to support consistent dissolution and drug release.
Manufacturing and handling choices are described to improve tablet content uniformity, including process changes for material transfer to reduce variability. Controlling bromocriptine particle size distribution, including narrowing via micronization, supports dissolution performance and the resulting pharmacokinetic targets.
Claims Coverage
The independent claim coverage is based on two independent dosage-form claims, each requiring absorption through gastric and/or intestinal mucosa, specified bromocriptine particle-size metrics, and pharmacokinetic Tmax windows under fasting and high fat fed conditions. The dependent claims further define bromocriptine as specific salts, specify excipient selections, add quantitative particle-size distribution constraints such as span, and restrict use to type 2 diabetes glycemic control in a subject.
Absorption through gastric and/or intestinal mucosa with particle-size controlled bromocriptine
The dosage form provides for absorption of a substantial amount of bromocriptine through the gastric and/or intestinal mucosa when administered to a subject, where bromocriptine has a DV90 less than 15 bcm and Dv10 of less than 2 bcm.
Pharmacokinetic Tmax targeting under fasting and high fat fed conditions
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 under fasting conditions, or between about 90 and about 120 minutes following oral administration under high fat fed conditions.
Absorption through gastric and/or intestinal mucosa with narrower particle-size metrics
The dosage form provides for absorption of a substantial amount of bromocriptine through the gastric and/or intestinal mucosa when administered to a subject, where bromocriptine has a Dv90 of about 15 bcm or lower, a Dv50 of about 8 bcm or lower and a Dv10 of about 3 bcm or lower.
Pharmacokinetic Tmax targeting under fasting and high fat fed conditions
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 under fasting conditions, or between about 90 and about 120 minutes following oral administration under high fat fed conditions.
Across both independent claims, the coverage centers on an oral bromocriptine dosage form that achieves substantial absorption through gastric and/or intestinal mucosa while meeting specified particle-size thresholds, and that produces defined Tmax windows after oral dosing under fasting versus high fat fed conditions. Dependent claims refine the bromocriptine form and excipient selection, further constrain particle-size distribution parameters such as span, and specify treatment of type 2 diabetes for glycemic control.
Stated Advantages
Provides for absorption of a substantial amount of bromocriptine through the gastric and/or intestinal mucosa.
Achieves a pharmacokinetic profile with Tmax between about 30 and about 60 minutes under fasting conditions and between about 90 and about 120 minutes under high fat fed conditions.
Improves content uniformity and reduces variability associated with drug release tied to particle size distribution.
Demonstrates improved dissolution/drug release behavior associated with controlled particle size distribution via micronization.
Documented Applications
Treating a type 2 diabetes patient by orally administering a dosage form comprising bromocriptine and excipients, where the dosage form is configured for glycemic control.
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