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Effects of Pump Pulsation on Hydrodynamic Properties and Dissolution Profiles in Flow-Through Dissolution Systems (USP 4)

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Abstract

Purpose

To clarify the effects of pump pulsation and flow-through cell (FTC) dissolution system settings on the hydrodynamic properties and dissolution profiles of model formulations.

Methods

Two FTC systems with different cell temperature control mechanisms were used. Particle image velocimetry (PIV) was used to analyze the hydrodynamic properties of test solutions in the flow-through dissolution test cell. Two pulsation pumps (semi-sine, full-sine) and a non-pulsatile pump were used to study the effects of varied flows on the dissolution profiles of United States Pharmacopeia standard tablets.

Results

PIV analysis showed periodic changes in the aligned upward fluid flow throughout the dissolution cell that was designed to reduce the temperature gradient during pump pulsation (0.5 s/pulse). The maximum instantaneous flow from the semi-sine pump was higher than that of the full-sine pump under all conditions. The flow from the semi-sine wave pump showed faster dissolution of salicylic acid and prednisone tablets than those from other pumps. The semi-sine wave pump flow showed similar dissolution profiles in the two FTC systems.

Conclusions

Variations in instantaneous fluid flow caused by pump pulsation that meets the requirements of pharmacopoeias are a factor that affects the dissolution profiles of tablets in FTC systems.

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Abbreviations

CFD:

Computational fluid dynamics

EP:

European pharmacopoeia

FTC:

Flow-through cell

ID:

Inside diameter

JP:

Japanese pharmacopoeia

PIV:

Particle imaging velocimetry

Tp :

Time phase of pump

USP:

United States pharmacopeia

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors would like to thank Mr. Shimizu and Mr. Nakatani (Dainippon Seiki Co., Ltd.) for making the DF-7 FTC system available. This work is partly supported by the Research on Regulatory Harmonization and Evaluation of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics from the Japan Agency for Medical Research and Development (AMED), and by a Health and Labour Sciences Research Grant from the Ministry of Health, Labour, and Welfare of Japan.

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Authors and Affiliations

  1. Division of Drugs, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo, 158-8501, Japan

    Hiroyuki Yoshida, Akemi Kuwana, Hiroko Shibata, Ken-ichi Izutsu & Yukihiro Goda

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  1. Hiroyuki Yoshida
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  2. Akemi Kuwana
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  3. Hiroko Shibata
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  4. Ken-ichi Izutsu
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  5. Yukihiro Goda
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Correspondence to Hiroyuki Yoshida.

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Yoshida, H., Kuwana, A., Shibata, H. et al. Effects of Pump Pulsation on Hydrodynamic Properties and Dissolution Profiles in Flow-Through Dissolution Systems (USP 4). Pharm Res 33, 1327–1336 (2016). https://doi.org/10.1007/s11095-016-1874-8

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  • DOI: https://doi.org/10.1007/s11095-016-1874-8

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