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Amorphous solid dispersions of tegoprazan and three different polymers: In vitro/in vivo evaluation of physicochemical properties

  • Polymer, Industrial Chemistry
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Abstract

Polymer-based amorphous solid dispersion (PASD) technology has attracted attention as one of the most feasible approaches for improving the solubility, dissolution rate, and bioavailability of insoluble drugs. Tegoprazan (TPZ) is a promising new drug used to treat gastroesophageal reflux disease with poor water solubility (∼0.03 mg/mL). This study developed novel PASD materials containing TPZ. Three polymers were used for this study: PVP, HPMCAS, and carbomer. The PASD powders were prepared via solvent evaporation at 50% drug loading. The physico-chemical properties of PASD solids were characterized using PXRD, MDSC, TGA, FT-IR, 1H SS-NMR, and stability testing. PASD powders fabricated with the neutral polymer PVP showed poor stability against drug crystallization. In contrast, those prepared using HPMCAS and carbomer showed no signs of crystallization even after three months of storage at 40oC/75% RH. A correlation between intermolecular interaction and physical stability was inferred for the TPZ PASD formulations. Amorphization of the crystalline TPZ with HPMCAS and carbomer resulted in a greatly increased in vitro dissolution rate. These two polymers showed similar performance, eliciting appreciable improvement in the in vivo absorption tests in rats. In summary, PASD formulations using acidic polymers (HPMCAS and carbomer) are novel formulations for improving the therapeutic effects of TPZ.

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Abbreviations

ASD:

amorphous solid dispersions

ATR:

attenuated total reflectance

AUC:

area under curve

BCS:

biopharmaceutical classification system

CCDC:

cambridge crystallographic data center

DSC:

differential scanning calorimetry

FT-IR:

Fourier transform-infrared

GERD:

gastroesophageal reflux disease

HPMCAS:

hydroxypropyl methylcellulose acetate succinate

MDSC:

modulated differential scanning calorimetry

PAA:

polyacrylic acid

PASD:

polymer-based amorphous solid dispersion

PDF:

pair distribution function

PPI:

proton pump inhibitors

PVP:

polyvinylpirrolidone

PXRD:

powder x-ray diffraction

SS-NMR:

solid-state nuclear magnetic resonance

TDA:

total diffraction analysis

TGA:

thermogravimetric analysis

Tg :

glass transition temperature

T m-calc g :

calculated glass transition temperature of ASD

T m-meas g :

measured glass transition temperature of ASD

TPZ:

tegoprazan

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Acknowledgements

This research was financially supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF-2020R1F1A106966813). This study was also supported by the Soonchunhyang University Research Fund.

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Authors and Affiliations

  1. Department of Medical Science, Soonchunhyang University, Asan, Chungnam, 31538, Korea

    Paul Kim, In-Seo Lee, Ji-Yoon Kim & Guang Jin Choi

  2. Department of Pharmaceutical Engineering, Soonchunhyang University, Asan, Chungnam, 31538, Korea

    Min-Jeong Lee & Guang Jin Choi

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  1. Paul Kim
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Correspondence to Guang Jin Choi.

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Amorphous solid dispersions of tegoprazan and three different polymers: In vitro/in vivo evaluation of physicochemical properties

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Kim, P., Lee, IS., Kim, JY. et al. Amorphous solid dispersions of tegoprazan and three different polymers: In vitro/in vivo evaluation of physicochemical properties. Korean J. Chem. Eng. 40, 986–998 (2023). https://doi.org/10.1007/s11814-022-1280-3

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