Antisolvent Recrystallization Strategy to Screen Appropriate Carriers to Stabilize Filgotinib Amorphous Solid Dispersions

Fuzheng Ren; Hanjing Sun; Lin Cui; Yike Si; Ning Chen; Guobin Ren; Qiufang Jing

doi:10.1016/j.xphs.2018.02.008

Antisolvent Recrystallization Strategy to Screen Appropriate Carriers to Stabilize Filgotinib Amorphous Solid Dispersions

J Pharm Sci. 2018 Jun;107(6):1624-1632. doi: 10.1016/j.xphs.2018.02.008. Epub 2018 Feb 16.

Authors

Fuzheng Ren¹, Hanjing Sun², Lin Cui², Yike Si², Ning Chen², Guobin Ren², Qiufang Jing³

Affiliations

¹ Laboratory of Pharmaceutical Crystal Engineering & Technology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: fzren@ecust.edu.cn.
² Laboratory of Pharmaceutical Crystal Engineering & Technology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
³ Laboratory of Pharmaceutical Crystal Engineering & Technology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.

PMID: 29454623
DOI: 10.1016/j.xphs.2018.02.008

Abstract

Drugs in amorphous solid dispersions (ASDs) are highly dispersed in hydrophilic polymeric carriers, which also help to restrain recrystallization and stabilize the ASDs. In this study, microscopic observation after antisolvent recrystallization was developed as a rapid screening method to select appropriate polymers for the initial design filgotinib (FTN) ASDs. Using solvent evaporation, FTN ASDs with the polymers were prepared, and accelerated experimentation validated this screening method. Fourier-transform infrared spectroscopy, Raman scattering, and nuclear magnetic resonance revealed hydrogen-bonding formation in the drug-polymer binary system, which was critical for ASDs stabilization. A Flory-Huggins interaction parameter and water sorption isotherms were applied to evaluate the strength of the interaction between FTN and the polymers. The dissolution rate was also significantly improved by ASDs formulation, and the presence of the polymers exerted solubilization effects. These results suggested the efficacy of this screening method as a preliminary tool for polymer selection in ASDs design.

Keywords: amorphous solid dispersions; filgotinib; interaction; polymers; screening method.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Crystallization
Drug Carriers / chemistry*
Drug Stability
Excipients / chemistry*
Hypromellose Derivatives / chemistry
Janus Kinase 1 / antagonists & inhibitors*
Polymers / chemistry*
Povidone / chemistry
Protein Kinase Inhibitors / administration & dosage
Protein Kinase Inhibitors / chemistry*
Pyridines / administration & dosage
Pyridines / chemistry*
Solubility
Triazoles / administration & dosage
Triazoles / chemistry*

Substances

Drug Carriers
Excipients
GLPG0634
Polymers
Protein Kinase Inhibitors
Pyridines
Triazoles
Hypromellose Derivatives
Janus Kinase 1
Povidone