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Altered Media Flow and Tablet Position as Factors of How Air Bubbles Affect Dissolution of Disintegrating and Non-disintegrating Tablets Using a USP 4 Flow-Through Cell Apparatus

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Abstract

This study investigated how air bubbles in media affect tablet dissolution in a flow-through cell system (USP 4) using disintegrating (USP prednisone) and non-disintegrating (USP salicylic acid) tablets. Cell hydrodynamics were studied using particle image velocimetry (PIV) and computational fluid dynamics (CFD). The PIV analysis showed periodic changes in the local flow corresponding to the discharge and suction of the pump cycles. The absence of prior deaeration induced small air bubbles in the media and lower maximum flow during the cycle, explaining the slower dissolution of the USP salicylic acid tablets. Bubbles, occurring during the USP prednisone tablets study, induced the transition of floating disintegrated particles towards the cell outlet, whereas the particles precipitated to form a white layer on the glass beads used in the study with prior deaeration. CFD analysis showed local flow variation in multiple positions of small (ID 12 mm) and large (ID 22.6 mm) cells, explaining the different rates of dissolution of prednisone tablet particles depending on their distribution. These results emphasize the importance of prior deaeration in dissolution studies using a flow-through system. Bubbles in the flow-through cell system affected tablet dissolution by reducing the area in contact with the media (wettability), lowering the maximum instantaneous flow (pressure buffering), and altering the position of disintegrated particles in the cell.

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Funding

This work was partly supported by the Research on Regulatory Harmonization and Evaluation of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics of the Japan Agency for Medical Research and Development (AMED) under Grant Number JP19mk0101130.

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Authors and Affiliations

  1. Division of Drugs, National Institute of Health Sciences, 3-25-26, Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan

    Hiroyuki Yoshida, Yasuhiro Abe & Ken-ichi Izutsu

  2. Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Tokyo, Japan

    Keita Teruya, Takayuki Furuishi, Kaori Fukuzawa & Etsuo Yonemochi

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  1. Hiroyuki Yoshida
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  2. Keita Teruya
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  3. Yasuhiro Abe
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Correspondence to Hiroyuki Yoshida.

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Yoshida, H., Teruya, K., Abe, Y. et al. Altered Media Flow and Tablet Position as Factors of How Air Bubbles Affect Dissolution of Disintegrating and Non-disintegrating Tablets Using a USP 4 Flow-Through Cell Apparatus. AAPS PharmSciTech 22, 227 (2021). https://doi.org/10.1208/s12249-021-02117-4

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