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Micronization of a poorly water-soluble drug, fenofibrate, via supercritical-fluid-assisted spray-drying

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Abstract

Purpose

In the present study, fenofibrate (a model drug with poor aqueous solubility) was micronized using the supercritical-fluid-assisted spray-drying (SA-SD) process to improve dissolution and biopharmaceutical property.

Methods

Solid-state characterizations including particle size analysis and dissolution test were carried out. To identify the main effects of SA-SD process parameters (such as pressure, temperature, concentration of drug solution, supercritical carbon dioxide (SC-CO2) injection rate, and drug solution injection rate) on the morphology and particle size distribution of micronized fenofibrate particles, a 27−3IV fractional factorial screening design was employed. Moreover, the effect of improved dissolution rate via micronization using SA-SD technology on the biopharmaceutical properties of fenofibrate was evaluated in a pharmacokinetic (PK) study in Sprague–Dawley rats.

Results

The results of the screening design showed that the mean particle size and distribution can be controlled by manipulating the drug solution concentration and CO2 injection rate. The SA-SD process resulted in a significant decrease in mean particle size (1.8–8.33 μm), as compared with that of unprocessed fenofibrate (24.2 ± 0.8 μm). There was a significant enhancement in the dissolution rate of micronized fenofibrate particles smaller than 5 μm compared to that of unprocessed fenofibrate. Moreover, an in vivo PK study in Sprague–Dawley rats showed that the increased dissolution rate improved biopharmaceutical properties (larger area under the curve and maximum serum concentration) of micronized fenofibrate than those of unprocessed fenofibrate.

Conclusion

Therefore, the SA-SD process is a useful micronization technology for improving both physicochemical and biopharmaceutical properties of poorly water-soluble drugs.

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Acknowledgements

This research was supported by the Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education (2016R1A6A1A03007648). This work was supported by the Mid-Career Researcher Program (No. NRF-2021R1A2C2008834) and Basic Research Infrastructure Support Program (University-Centered Labs-2018R1A6A1A03023718) through the National Research Foundation of Korea (NRF) funded by the Korean government (MSIT). This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2020R1A2C4002166).

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  1. Jeong-Soo Kim and Heejun Park have contributed equally to this manuscript.

Authors and Affiliations

  1. Dong-A ST Co. Ltd, Giheung-gu, Yongin, Gyeonggi, 446-905, Republic of Korea

    Jeong-Soo Kim

  2. College of Pharmacy, Duksung Women’s University, 33, Samyangro 144-gil, Dobong-gu, Seoul, 01369, Republic of Korea

    Heejun Park & Kyu-Tae Kang

  3. College of Pharmacy, Pusan National University, 2, Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan, 46241, Republic of Korea

    Eun-Sol Ha & Min-Soo Kim

  4. Yonsei Institute of Pharmaceutical Sciences & College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon, 21983, Korea

    Sung-Joo Hwang

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  1. Jeong-Soo Kim
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Correspondence to Min-Soo Kim or Sung-Joo Hwang.

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All authors (J.-S. Kim, H. Park, K.-T. Kang, E.-S. Ha, M.-S. Kim, and S.-J. Hwang) declare no conflict of interest.

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The animal study was conducted according to the guidelines of the Care and Use of Laboratory Animals, and approved by the Institutional Review Board of the nonclinical contract research organization, KPC laboratory (Approved Protocol Code: I-1708186, Date of Approval: 29 August 2017).

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Kim, JS., Park, H., Kang, KT. et al. Micronization of a poorly water-soluble drug, fenofibrate, via supercritical-fluid-assisted spray-drying. J. Pharm. Investig. 52, 353–366 (2022). https://doi.org/10.1007/s40005-022-00565-z

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