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Screen for Inhibitors of Crystal Growth to Identify Desirable Carriers for Amorphous Solid Dispersions Containing Felodipine

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Abstract

The solvent-shift method was used to identify appropriate polymers that inhibit the growth of felodipine crystals by monitoring particle size in supersaturated drug solutions in the presence of different polymers. We speculated that there would be an intermolecular interaction between the selected polymer (zein) and felodipine by extrapolating the inhibitory effect on crystal growth and then used the selected polymer as a carrier to prepare solid dispersions. The formulations were characterized by crystalline properties, thermodynamics of mixing, dissolution behavior, and physical stability. Powder x-ray diffraction and differential scanning calorimetry experiments indicated that amorphous solid dispersions were formed when the proportion of felodipine was < 30% (w/w). Stability tests showed that a solid dispersion with 20% felodipine remained in an amorphous state and was stable under accelerated storage conditions for 6 months. The dissolution rates of solid dispersions were significantly greater than those of the active pharmaceutical ingredient or physical mixtures. Analysis by Fourier-transform infrared spectroscopy and Raman microspectroscopy indicated the formation of intermolecular interactions between zein and felodipine. The study demonstrates the successful application of the chosen polymer as a carrier in solid dispersions and validates the concept of extrapolating the inhibitory effect on crystal growth to intermolecular interactions.

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Acknowledgments

This work was supported by the Baoshan District Committee of Science and Technology (grant no. bkw2014131) and the National Natural Science Foundation of China (grant no. 21576080).

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Authors and Affiliations

  1. Laboratory of Pharmaceutical Crystal Engineering & Technology, School of Pharmacy, East China University of Science and Technology, 363#, No. 130, Meilong Rd, Shanghai, 200237, China

    Jinping Fu, Lin Cui, Congbin Yang, Hui Xiong, Guobin Ren, Qiufang Jing & Fuzheng Ren

  2. Shanghai Key Lab New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China

    Xingyuan Ma

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  1. Jinping Fu
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  2. Lin Cui
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Correspondence to Fuzheng Ren.

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Fu, J., Cui, L., Yang, C. et al. Screen for Inhibitors of Crystal Growth to Identify Desirable Carriers for Amorphous Solid Dispersions Containing Felodipine. AAPS PharmSciTech 19, 1231–1242 (2018). https://doi.org/10.1208/s12249-017-0942-7

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  • DOI: https://doi.org/10.1208/s12249-017-0942-7

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