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An economically advantageous amorphous solid dispersion of the fixed combination of lopinavir and ritonavir

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Abstract

Purpose

Solid dispersion strategies have recently been used to increase the solubility and bioavailability of poorly soluble drugs. Among these various strategies for solid dispersion, the method using polymers and adsorbents can improve the solubility and bioavailability of poorly soluble drugs and provide excellent powder fluidity. Therefore, the purpose of this study was to prepare and evaluate an amorphous solid dispersion (ASD) composed of LPV, RTV, polymer and adsorbent for oral administration.

Methods

The ASD powder was manufactured by dispersing LPV and RTV in a polymer solution and adsorbing the dispersion with an adsorbent. The ASD was characterized using physical characterization, differential scanning calorimetry, Fourier transform-infrared, powder X-ray diffractometer, in vitro release, and cytotoxicity tests. And ASD performed pharmacokinetic studies in rats.

Results

The ASD increased the solubility of raw LPV and RTV by 5.71 times and 4.38 times, respectively. When copovidone was used as the polymer in the ASD, the solubility was maintained for 10 days in the solubility kinetic test, whereas the solubility of LPV decreased from day 2 due to precipitation in an ASD without copovidone. The adsorbent, Florite PS-10, had a flowability suitable for the ASD powder, and the ASD did not increase cell cytotoxicity. In pharmacokinetic study, ASD showed 1186.51% relative bioavailability compared to raw LPV and about 2.1-fold increase than commercial products after oral administration.

Conclusion

Manufacture of an ASD powder using Florite PS-10 and copovidone as an oral administration formulation of LPV and RTV could be a new effective drug delivery system for human immunodeficiency virus treatment.

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Acknowledgements

We thank Korea United Pharm Inc. (Seoul, Korea) for providing materials for this study.

Funding

This work was supported by the Basic Science Research Program (2019R1A2C10786102) through the National Research Foundation of Korea (NRF).

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Authors and Affiliations

  1. College of Pharmacy, Chungnam National University, 99, Daehak-ro, Daejeon, 31434, South Korea

    Taek-Seon Yun, Minwoo Jung, Ki-Hyun Bang, Minki Jin, Hyelim Yoo, Jong-Hee Won, Bomin Song, Yu-Rim Hwang & Cheong-Weon Cho

  2. Jeonbuk Branch, Human Health Risk Assessment Center, Korea Institute of Toxicology (KIT), Jeongeup, 53212, South Korea

    Hong-Ki Lee

  3. Center for Companion Animal New Drug Development, Jeonbuk Branch, Korea Institute of Toxicology (KIT), Jeongeup, 53212, South Korea

    Hong-Ki Lee

  4. Department of Bio-Health Convergence, Kangwon National University, Chuncheon, 24341, South Korea

    Jong-Suep Baek

  5. Department of Bio-Functional Materials, Kangwon National University, 346 Hwangjo-Gil, Dogye-Eup, Samcheok-Si, 25949, South Korea

    Jong-Suep Baek

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  1. Taek-Seon Yun
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  2. Minwoo Jung
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Corresponding authors

Correspondence to Jong-Suep Baek or Cheong-Weon Cho.

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Conflict of interest

All authors (T.-S. Yun, M. Jung, K.-H. Bang, H.-K. Lee, M. Jin, H. Yoo, J.-H. Won, B. Song, Y.-R. Hwang, J.-S. Baek, and C.-W. Cho) declare that they have no conflict of interest.

Research involving human and animal rights

Animal studies were performed according to the protocol approved by Chungnam National University Animal Hospital (202203 A-CNU-048, Daejeon, Korea).

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Yun, TS., Jung, M., Bang, KH. et al. An economically advantageous amorphous solid dispersion of the fixed combination of lopinavir and ritonavir. J. Pharm. Investig. 53, 549–561 (2023). https://doi.org/10.1007/s40005-023-00623-0

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