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Evaluating the Effect of Microcrystalline Cellulose Variations on Tablet Quality of Natural Plant Product Using a Design of Experiment Approach

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Abstract

Microcrystalline cellulose (MCC) of different grades from different manufacturers differ in particulate and powder properties significantly. The choice of MCC is important to the development of a tablet formulation with satisfactory quality. In this study, the effects of five different MCCs (KG 802, Pharmacel 102, MC 302, M 200, and PH 112) that had different compactibility and tablet disintegration on the tablet quality of two different natural plant products (NPPs) were evaluated systematically, including Crataegi Folium ethanol extract (CF-E) and Sarcandrae Herba water extract (SH-W). The result of D-optimal mixture designs demonstrated that KG 802 showed the best ability to improve compression properties and tensile strength, followed by Pharmacel 102, MC 302, and M 200. PH 112 did the weakest. However, MCCs of different grades had no different influence on the disintegration of NPP tablets. Similar results were found in the experiments of the two different NPP powders, suggesting the generalization of the finding. Moreover, KG 802-containing CF-E formulations showed the largest optimum region size, that is, the lowest production risk. The design space sizes of SH-W were hardly sensitive to the change of MCCs, due to the better tabletability. In conclusion, the properties of MCCs could transfer to the high NPP loading (70%) formulations, leading to the variations on the compression properties and tablet quality. The poorer the tabletability of NPP, the more obvious the variation. The result is promising for the use of MCC and the manufacturing of high drug-loading NPP tablets by direct compression.

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Data Availability

Data will be made available on request.

Abbreviations

MCC:

Microcrystalline cellulose

NPP:

Natural plant product

CF-E:

Crataegi Folium Ethanol extract

SH-W:

Sarcandrae Herba Water extract

FDA:

Food and Drug Administration

DC:

Direct compression

TS, σ:

Tensile strength

DT:

Disintegration time

ρ b :

Bulk density

ρ t :

Tapped density

ρ true :

True density

ε:

Porosity

D50:

Median particle size

LAC:

Spray-dried monohydrate lactose

DCPA:

Dicalcium phosphate anhydrate

CCS:

Croscarmellose sodium

MgSt:

Magnesium stearate

Py:

Yield pressure

R2 :

Coefficient of determination

Eq:

Equation

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Funding

This work was sponsored by the National Natural Science Foundation of China (82003958); The Natural Science Foundation project of Shanghai (23ZR1463500); National Drug Standard Improvement Project 2022 (2022Y26); The Budgetary project of Shanghai University of Traditional Chinese Medicine (2020LK022).

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Authors and Affiliations

  1. School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No.1200, Cai-Lun Road, Pudong District, Shanghai, 201203, People’s Republic of China

    Haiyue Zhao, Zhenda Liu & Lan Shen

  2. Engineering Research Center of Modern Preparation Technology of Traditional Chinese Medicine of Ministry of Education, Shanghai University of Traditional Chinese Medicine, No.1200, Cai-Lun Road, Pudong District, Shanghai, 201203, People’s Republic of China

    Chuting Shi & Lijie Zhao

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  1. Haiyue Zhao
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  2. Chuting Shi
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  3. Zhenda Liu
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  4. Lijie Zhao
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  5. Lan Shen
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Contributions

Haiyue Zhao: methodology, data curation, writing—original draft, investigation. Chuting Shi: methodology, investigation. Zhenda Liu: software, investigation. Lijie Zhao: conceptualization, methodology, writing—review & editing, supervision, funding acquisition. Lan Shen: conceptualization, writing—review & editing, resources, supervision, funding acquisition.

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Correspondence to Lijie Zhao or Lan Shen.

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Zhao, H., Shi, C., Liu, Z. et al. Evaluating the Effect of Microcrystalline Cellulose Variations on Tablet Quality of Natural Plant Product Using a Design of Experiment Approach. AAPS PharmSciTech 24, 113 (2023). https://doi.org/10.1208/s12249-023-02556-1

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