Using acetone/water binary solvent to enhance the stability and bioavailability of spray dried enzalutamide/HPMC-AS solid dispersions

Xiaoting Zhang; Qiuhong Rao; Zhenwen Qiu; Yisheng Lin; Lei Zhang; Qingzhong Hu; Tingting Chen; Zhimin Ma; Hanlu Gao; Dandong Luo; Jiaqi Zhao; Defang Ouyang; Zhenyu Jason Zhang; Qingguo Li

doi:10.1016/j.xphs.2020.10.010

Using acetone/water binary solvent to enhance the stability and bioavailability of spray dried enzalutamide/HPMC-AS solid dispersions

Xiaoting Zhang, Qiuhong Rao, Zhenwen Qiu, Yisheng Lin, Lei Zhang, Qingzhong Hu, Tingting Chen, Zhimin Ma, Hanlu Gao, Dandong Luo, Jiaqi Zhao, Defang Ouyang, Zhenyu Jason Zhang, Qingguo Li^*

^*Corresponding author for this work

Chemical Engineering

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Abstract

We demonstrated a facile approach, by adjusting the solvent ratio of water/acetone binary mixture, to alter the intermolecular interactions between Enzalutamide (ENZ) and hydroxypropyl methylcellulose acetate succinate (HPMC-AS) for spray drying process, which can be readily implemented to produce spray-dried dispersions (SDD) with enhanced stability and bioavailability. The prepared SDD of ENZ/ HPMC-AS were examined systematically in terms of particle size, morphology, dissolution, solubility, stability, and bioavailability. Our results show that the introduction of water (up to 30% volume fraction) can effectively reduce the hydrodynamic diameter of HPMC-AS from approximately 220 nm to 160 nm (a reduction of c.a. 20%), which increases the miscibility of the drug and polymer, delaying or inhibiting the crystallization of ENZ during the spray drying process, resulting in a homogeneous amorphous phase. The benefits of using acetone/water binary mixture were subsequently evidenced by an increased spe- cific surface area, improved dissolution profile and relative bioavailability, enhanced stability, and elevated drug release rate. This fundamental finding underpins the great potential of using binary mixture for spray drying process to process active pharmaceutical ingredients (APIs) that are otherwise challenging to handle.

Original language	English
Pages (from-to)	1160-1171
Number of pages	12
Journal	Journal of Pharmaceutical Sciences
Volume	110
Issue number	3
Early online date	10 Oct 2020
DOIs	https://doi.org/10.1016/j.xphs.2020.10.010
Publication status	Published - Mar 2021

Bibliographical note

Funding Information:
The authors acknowledge financial support from the Medical Scientific Research Foundation of Guangdong Province of China (grant numbers B2018072); the Guangdong Science and Technology Program (grant number 2017ZC0140); the Overseas Scholars of Guangzhou University of Chinese Medicine (Torch program); Department of Science and Technology of Guangdong Province (2015A020211024) and Natural Science Foundation of Guangdong Province (2019A1515012118).

The authors would like to thank Dr. Qiuping Guo of Guangzhou General Pharmaceutical Institute for providing experimental guidance. We also acknowledge Prof. Jianfeng Hu, Dr. Yan Cai, and Dr. Qian Sun of South China University of Technology for providing technical guidance with SEM and XRPD.

Publisher Copyright:
© 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Keywords

Spray drying
Poorly water-soluble drug
Particle size
Amorphous solid dispersion
Drug-excipient interaction

ASJC Scopus subject areas

Pharmaceutical Science

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ZhangX2021UsingAccepted author manuscript, 433 KBLicence: Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND)

Cite this

Zhang, X., Rao, Q., Qiu, Z., Lin, Y., Zhang, L., Hu, Q., Chen, T., Ma, Z., Gao, H., Luo, D., Zhao, J., Ouyang, D., Zhang, Z. J., & Li, Q. (2021). Using acetone/water binary solvent to enhance the stability and bioavailability of spray dried enzalutamide/HPMC-AS solid dispersions. Journal of Pharmaceutical Sciences, 110(3), 1160-1171. Advance online publication. https://doi.org/10.1016/j.xphs.2020.10.010

@article{933acd95fec04d969abae2d2bdb63857,

title = "Using acetone/water binary solvent to enhance the stability and bioavailability of spray dried enzalutamide/HPMC-AS solid dispersions",

abstract = "We demonstrated a facile approach, by adjusting the solvent ratio of water/acetone binary mixture, to alter the intermolecular interactions between Enzalutamide (ENZ) and hydroxypropyl methylcellulose acetate succinate (HPMC-AS) for spray drying process, which can be readily implemented to produce spray-dried dispersions (SDD) with enhanced stability and bioavailability. The prepared SDD of ENZ/ HPMC-AS were examined systematically in terms of particle size, morphology, dissolution, solubility, stability, and bioavailability. Our results show that the introduction of water (up to 30% volume fraction) can effectively reduce the hydrodynamic diameter of HPMC-AS from approximately 220 nm to 160 nm (a reduction of c.a. 20%), which increases the miscibility of the drug and polymer, delaying or inhibiting the crystallization of ENZ during the spray drying process, resulting in a homogeneous amorphous phase. The benefits of using acetone/water binary mixture were subsequently evidenced by an increased spe- cific surface area, improved dissolution profile and relative bioavailability, enhanced stability, and elevated drug release rate. This fundamental finding underpins the great potential of using binary mixture for spray drying process to process active pharmaceutical ingredients (APIs) that are otherwise challenging to handle.",

keywords = "Spray drying, Poorly water-soluble drug, Particle size, Amorphous solid dispersion, Drug-excipient interaction",

author = "Xiaoting Zhang and Qiuhong Rao and Zhenwen Qiu and Yisheng Lin and Lei Zhang and Qingzhong Hu and Tingting Chen and Zhimin Ma and Hanlu Gao and Dandong Luo and Jiaqi Zhao and Defang Ouyang and Zhang, {Zhenyu Jason} and Qingguo Li",

note = "Funding Information: The authors acknowledge financial support from the Medical Scientific Research Foundation of Guangdong Province of China (grant numbers B2018072); the Guangdong Science and Technology Program (grant number 2017ZC0140); the Overseas Scholars of Guangzhou University of Chinese Medicine (Torch program); Department of Science and Technology of Guangdong Province (2015A020211024) and Natural Science Foundation of Guangdong Province (2019A1515012118). The authors would like to thank Dr. Qiuping Guo of Guangzhou General Pharmaceutical Institute for providing experimental guidance. We also acknowledge Prof. Jianfeng Hu, Dr. Yan Cai, and Dr. Qian Sun of South China University of Technology for providing technical guidance with SEM and XRPD. Publisher Copyright: {\textcopyright} 2020 American Pharmacists Association{\textregistered}. Published by Elsevier Inc. All rights reserved.",

year = "2021",

month = mar,

doi = "10.1016/j.xphs.2020.10.010",

language = "English",

volume = "110",

pages = "1160--1171",

journal = "Journal of Pharmaceutical Sciences",

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Zhang, X, Rao, Q, Qiu, Z, Lin, Y, Zhang, L, Hu, Q, Chen, T, Ma, Z, Gao, H, Luo, D, Zhao, J, Ouyang, D, Zhang, ZJ & Li, Q 2021, 'Using acetone/water binary solvent to enhance the stability and bioavailability of spray dried enzalutamide/HPMC-AS solid dispersions', Journal of Pharmaceutical Sciences, vol. 110, no. 3, pp. 1160-1171. https://doi.org/10.1016/j.xphs.2020.10.010

TY - JOUR

T1 - Using acetone/water binary solvent to enhance the stability and bioavailability of spray dried enzalutamide/HPMC-AS solid dispersions

AU - Zhang, Xiaoting

AU - Rao, Qiuhong

AU - Qiu, Zhenwen

AU - Lin, Yisheng

AU - Zhang, Lei

AU - Hu, Qingzhong

AU - Chen, Tingting

AU - Ma, Zhimin

AU - Gao, Hanlu

AU - Luo, Dandong

AU - Zhao, Jiaqi

AU - Ouyang, Defang

AU - Zhang, Zhenyu Jason

AU - Li, Qingguo

N1 - Funding Information: The authors acknowledge financial support from the Medical Scientific Research Foundation of Guangdong Province of China (grant numbers B2018072); the Guangdong Science and Technology Program (grant number 2017ZC0140); the Overseas Scholars of Guangzhou University of Chinese Medicine (Torch program); Department of Science and Technology of Guangdong Province (2015A020211024) and Natural Science Foundation of Guangdong Province (2019A1515012118). The authors would like to thank Dr. Qiuping Guo of Guangzhou General Pharmaceutical Institute for providing experimental guidance. We also acknowledge Prof. Jianfeng Hu, Dr. Yan Cai, and Dr. Qian Sun of South China University of Technology for providing technical guidance with SEM and XRPD. Publisher Copyright: © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

PY - 2021/3

Y1 - 2021/3

N2 - We demonstrated a facile approach, by adjusting the solvent ratio of water/acetone binary mixture, to alter the intermolecular interactions between Enzalutamide (ENZ) and hydroxypropyl methylcellulose acetate succinate (HPMC-AS) for spray drying process, which can be readily implemented to produce spray-dried dispersions (SDD) with enhanced stability and bioavailability. The prepared SDD of ENZ/ HPMC-AS were examined systematically in terms of particle size, morphology, dissolution, solubility, stability, and bioavailability. Our results show that the introduction of water (up to 30% volume fraction) can effectively reduce the hydrodynamic diameter of HPMC-AS from approximately 220 nm to 160 nm (a reduction of c.a. 20%), which increases the miscibility of the drug and polymer, delaying or inhibiting the crystallization of ENZ during the spray drying process, resulting in a homogeneous amorphous phase. The benefits of using acetone/water binary mixture were subsequently evidenced by an increased spe- cific surface area, improved dissolution profile and relative bioavailability, enhanced stability, and elevated drug release rate. This fundamental finding underpins the great potential of using binary mixture for spray drying process to process active pharmaceutical ingredients (APIs) that are otherwise challenging to handle.

AB - We demonstrated a facile approach, by adjusting the solvent ratio of water/acetone binary mixture, to alter the intermolecular interactions between Enzalutamide (ENZ) and hydroxypropyl methylcellulose acetate succinate (HPMC-AS) for spray drying process, which can be readily implemented to produce spray-dried dispersions (SDD) with enhanced stability and bioavailability. The prepared SDD of ENZ/ HPMC-AS were examined systematically in terms of particle size, morphology, dissolution, solubility, stability, and bioavailability. Our results show that the introduction of water (up to 30% volume fraction) can effectively reduce the hydrodynamic diameter of HPMC-AS from approximately 220 nm to 160 nm (a reduction of c.a. 20%), which increases the miscibility of the drug and polymer, delaying or inhibiting the crystallization of ENZ during the spray drying process, resulting in a homogeneous amorphous phase. The benefits of using acetone/water binary mixture were subsequently evidenced by an increased spe- cific surface area, improved dissolution profile and relative bioavailability, enhanced stability, and elevated drug release rate. This fundamental finding underpins the great potential of using binary mixture for spray drying process to process active pharmaceutical ingredients (APIs) that are otherwise challenging to handle.

KW - Spray drying

KW - Poorly water-soluble drug

KW - Particle size

KW - Amorphous solid dispersion

KW - Drug-excipient interaction

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U2 - 10.1016/j.xphs.2020.10.010

DO - 10.1016/j.xphs.2020.10.010

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SN - 0022-3549

VL - 110

SP - 1160

EP - 1171

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

IS - 3

ER -

Using acetone/water binary solvent to enhance the stability and bioavailability of spray dried enzalutamide/HPMC-AS solid dispersions

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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