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Mesoporous Silica Carrier-Based Composites for Taste-Masking of Bitter Drug: Fabrication and Palatability Evaluation

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Abstract

Abstract. Palatability is one of the most critical characteristics of oral preparations. Therefore, the exploration of new techniques to mask the aversive taste of drugs is in continuous demand. In this study, we fabricated and characterized composites based on mesoporous silica (MPS) that consisted of MPS, a bitter drug, and release regulators. We conducted a palatability evaluation to assess the taste-masking efficacy of the composites. The composites were prepared using the dry impregnation method combined with hot-melt extrusion. Morphology and components distribution in composites were characterized by scanning electron microscopy, confocal laser scanning microscopy, X-ray photoelectron spectroscopy, powder flow properties evaluation, and nitrogen-sorption measurement. The results demonstrated that drugs mainly existed in the inner pore of composites, and release regulators existed in the inner pore and covered the composites’ surface. Interactions among the composite components were studied using powder X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy. The drug loaded into the composites was amorphous, and an intermolecular interaction occurred between the drug and the MPS. Taste-masked composites significantly reduced drug release levels under mouth conditions; thus, they prevented the interaction of the dissolved drug with taste receptors and improved palatability. An electronic tongue evaluation and a human taste panel assessment confirmed the better palatability of taste-masked composites. Moreover, the desired drug release behavior can be adjusted by choosing an appropriate release regulator, with stronger hydrophobicity of release regulators resulting in slower drug release. This work has provided new insights into taste-masking strategies for drugs with unpleasant tastes.

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Abbreviations

API:

Active pharmaceutical ingredients

OP:

Oseltamivir phosphate

MPS:

Mesoporous silica

GD:

Glycerol distearate

GB:

Glycerol behenate

HVO:

Hydrogenated vegetable oil

MPS-OP:

MPS-OP composite

MPS-OP-M:

MPS-OP physical mixture

MPS-OP-GD:

(MPS-OP)-GD composite

MPS-OP-GD-M:

(MPS-OP)-GD physical mixture

MPS-OP-GB:

(MPS-OP)-GB composite

MPS-OP-GB-M:

(MPS-OP)-GB physical mixture

MPS-OP-HVO:

(MPS-OP)-HVO composite

MPS-OP-HVO-M:

(MPS-OP)-HVO physical mixture

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Acknowledgments

The authors thank Dr Gaopin Yang (Pharmaceutical Processing Solution Co., Ltd, China) for assisting us with the preparation of composites using a hot-melt extruder.

Funding

The China Postdoctoral Science Foundation (2020M672078), National Major Scientific and Technological Special Project for “Significant New Drugs Development” during the Thirteenth Five-Year Plan Period (2018ZX09721003), Shandong Provincial Natural Science Foundation (ZR2021QH360), and TaiShan Industrial Experts Programme (2019TSCYCX-31) financially supported this work.

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Authors and Affiliations

  1. Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan, 250012, People’s Republic of China

    Weifeng Zhang & Guangxi Zhai

  2. Department of Pharmaceutical Development, Shandong Dyne Marine Biopharmaceutical Limited Corporation, 18 Fuyuan Nnalu, Rongcheng, 264300, People’s Republic of China

    Weifeng Zhang, Chaoqiang Xiao, Xueping Wu & Shuwang He

  3. Beijing Dyne High-tech Institute of Medicine for Children Limited Corporation, Beijing, 100176, China

    Weifeng Zhang, Guoxiang Li, Chaoqiang Xiao, Xin Chang, Ying Sun, Weiping Fan, Bing Tian, Di Gao, Yao Xiao & Shuwang He

  4. Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China

    Chaoqiang Xiao

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  1. Weifeng Zhang
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  2. Guoxiang Li
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Contributions

Conception and design of work, W.F.Z., S.W.H., and G.X.Z.; experimental execution, W.F.Z., G.X.L., X.C., Y.S., W.P.F., and X.P.W.; analysis and interpretation of the data, W.F.Z., X.P.W., C.Q.X., Y.X., B.T., D.G., S.W.H., and G.X.Z; drafting of the manuscript, W.F.Z.; revision of the manuscript, W.F.Z., C.Q.X., S.W.H., and G.X.Z; supervision, S.W.H., and G.X.Z; funding acquisition, W.F.Z., S.W.H., and G.X.Z.

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Correspondence to Shuwang He or Guangxi Zhai.

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Zhang, W., Li, G., Xiao, C. et al. Mesoporous Silica Carrier-Based Composites for Taste-Masking of Bitter Drug: Fabrication and Palatability Evaluation. AAPS PharmSciTech 23, 75 (2022). https://doi.org/10.1208/s12249-022-02227-7

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