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Publication Number
US-11510921-B2
Publication Date
2022-11-29
Expiration Date
Abstract
The present disclosure describes pharmaceutical formulations of bromocriptine and methods of manufacturing and using such formulations. The formulations are useful for treating physiological disorders including improving glycemic control in the treatment of type 2 diabetes. Also disclosed is synthesis of bromocriptine citrate, and compositions and dosage forms containing bromocriptine citrate.
Core Innovation
The invention relates to pharmaceutical formulations comprising bromocriptine citrate and excipients, wherein the excipients comprise 0.1-10% of a triglyceride or hydrogenated castor oil, 30-90% mannitol, and 0.1-10% citric acid, and the pharmaceutical formulation is substantially free of magnesium or lactose. The formulation provides a dose of between 0.1 and 9.6 mg bromocriptine.
The formulation is described in terms of improved water solubility, heat, water, and aqueous stability, including comparative behavior versus bromocriptine mesylate. The disclosed approach addresses bromocriptine degradation, including bromocriptinine, and browning associated with formulation components and storage.
In specific embodiments, the bromocriptine is micronized and has a Dv90 of about 10 µm or lower. Example reports include tablet formulation blends using citric acid with bromocriptine and describe recorded physical properties and dissolution results for multiple formulations.
Claims Coverage
The independent claims cover two core formulations. Across them, the inventive features are defined by bromocriptine citrate with specified excipient ranges, exclusion of magnesium or lactose, and in one claim micronization with a Dv90 constraint.
Bromocriptine citrate excipient system with triglyceride, mannitol, and citric acid
A pharmaceutical formulation comprising bromocriptine citrate in an amount that provides a dose of between 0.1 and 9.6 mg bromocriptine, and excipients comprising 0.1-10% of a triglyceride, 30-90% mannitol, and 0.1-10% citric acid.
Substantially free of magnesium or lactose
The pharmaceutical formulation is substantially free of magnesium or lactose.
Hydrogenated castor oil triglyceride with micronized bromocriptine and Dv90 constraint
A pharmaceutical formulation comprising 0.1-9.6 mg bromocriptine citrate and excipients comprising 0.1-10% hydrogenated castor oil, 30-90% mannitol, and 0.1-10% citric acid, wherein the bromocriptine is micronized and has a Dv90 of about 10 µm or lower.
Free of magnesium or lactose
The pharmaceutical formulation is free of magnesium or lactose.
Together, the claims cover bromocriptine citrate formulations using defined ranges of triglyceride, mannitol, and citric acid, while excluding magnesium and lactose, and in one claim further requiring micronization and a Dv90 constraint.
Stated Advantages
Improved water solubility.
Improved heat, water, and aqueous stability.
Reduces bromocriptine degradation, including formation of bromocriptinine, and browning.
Provides aqueous stability versus bromocriptine mesylate.
Increased water solubility compared with a traditional bromocriptine mesylate formulation.
Improved heat/humidity stability compared with a traditional bromocriptine mesylate formulation.
Documented Applications
Treatment of metabolic disorders using the disclosed pharmaceutical formulations, including timed dosing after waking for a metabolic disorder such as type 2 diabetes mellitus and glycemic control.
Comparative testing of bromocriptine citrate formulations versus a traditional bromocriptine mesylate formulation, including heat/humidity stability and water solubility.
Tablet formulation contexts with recorded physical properties and dissolution testing results for multiple tablet formulations using citric acid and bromocriptine.
Submission notes for animal studies based on dissolution behavior across several formulations.
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