Mifepristone polymorph with enhanced solubility, dissolution and oral bioavailability

•Polymorphism in drugs may have direct medical effect.•For a drug, different polymorph has different solubility, one polymorph may be more active than another polymorph.•Good results could be obtained with simple method---screening polymorphs. Mifepristone is one of potent anti-progesterone agents,...

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Bibliographic Details
Published in:Steroids 2020-07, Vol.159, p.108649, Article 108649
Main Authors: Xu, Juan, Gong, Xiao-Fang, Li, Peng, Chen, Xiao-Feng, Wang, Hui-Ping, Ning, Li-Feng
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Biological Availability
Dissolution
Female
Hormone Antagonists - administration & dosage
Hormone Antagonists - chemistry
Hormone Antagonists - pharmacokinetics
Mifepristone
Mifepristone - administration & dosage
Mifepristone - chemistry
Mifepristone - pharmacokinetics
Molecular Conformation
Oral bioavailability
Polymorphism
Rats
Rats, Sprague-Dawley
Solubility
Solvent-free polymorph
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Summary:•Polymorphism in drugs may have direct medical effect.•For a drug, different polymorph has different solubility, one polymorph may be more active than another polymorph.•Good results could be obtained with simple method---screening polymorphs. Mifepristone is one of potent anti-progesterone agents, which binds to progesterone receptors and glucocorticoid receptors. Until now, there are a lot of research focusing on enhancing the solubility and oral bioavailability of Mifepristone. However, poor solubility and oral bioavailability has some undesirable consequences. In this work, Mifepristone in form D was discovered for the first time and characterized by PXRD, TGA, DSC, FT-IR, SEM and SS NMR. Form D was a metastable crystal type which manifested favorable stability under ambient conditions. Form D had better dissolution characteristic compared with commercial Mifepristone in 0.5% SDS solution. In addition, Mifepristone in form D exhibited a 1.43-fold higher peak plasma concentration (Cmax) and 1.46-fold higher area under the curve (AUC) in rats. The work in this paper is a complement to the present understanding of drug polymorphism on the in vitro and in vivo behavior, and establishes the ground work for future development of Mifepristone in form D as a promising drug for the market.
ISSN:0039-128X
1878-5867
DOI:10.1016/j.steroids.2020.108649