Skip to main content
SpringerLink
Log in

Protein Based Amorphous Solid Dispersion: a Case Study Investigating Different Whey Proteins at High Drug Loading

  • Original Research Article
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

Whey protein isolate (WPI) has previously been shown to be a promising new excipient for the development of amorphous solid dispersions (ASD) at a high drug loading of 50% (w/w). Whilst WPI is a protein mixture, comprising mainly the three proteins β-lactoglobulin (BLG), α-lactalbumin (ALA), casein glycomacropeptides (CGMP), the individual contributions of these three proteins to the overall performance of whey protein based ASDs has still not been investigated. In addition, the limitations of the technology at even higher drug loadings (i.e., more than 50%) have not yet been explored. In this study, BLG, ALA, CGMP and WPI were each prepared as ASDs with the two poorly water-soluble drugs (Compound A and Compound B) at 50%, 60% and 70% drug loadings.

Methods

Solid state characterization, dissolution rate and physical stability of the obtained samples were analyzed.

Results

All the obtained samples were amorphous and showed faster dissolution rates compared to the respective pure crystalline drugs. However, the BLG based formulations—at least for Compound A—were outperforming the other ASDs in terms of stability, dissolution enhancement and solubility increase.

Conclusion

Overall, the study confirmed that the investigated whey proteins showed their potential in developing ASDs even at high drug loadings of up to 70%.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Brough C, Williams RO. Amorphous solid dispersions and nano-crystal technologies for poorly water-soluble drug delivery. Int J Pharm. 2013;453(1):157–66. https://doi.org/10.1016/j.ijpharm.2013.05.061.

    Article  CAS  PubMed  Google Scholar 

  2. Grohganz H, et al. Refining stability and dissolution rate of amorphous drug formulations. Expert Opin Drug Deliv. 2014;11(6):977–89. https://doi.org/10.1517/17425247.2014.911728.

    Article  CAS  PubMed  Google Scholar 

  3. Moseson DE, Ning T, Su Y, Taylor LS. Formulation and processing strategies which underpin susceptibility to matrix crystallization in amorphous solid dispersions. J Pharm Sci. 2023;112(1):108–22. https://doi.org/10.1016/j.xphs.2022.03.020.

    Article  CAS  PubMed  Google Scholar 

  4. Bhattacharya S, Suryanarayanan R. Local mobility in amorphous pharmaceuticals-Characterization and implications on stability. J Pharm Sci. 2009;98(9):2935–53. https://doi.org/10.1002/jps.21728.

  5. Yu L. Amorphous pharmaceutical solids: preparation, characterization and stabilization. Adv Drug Deliv Rev. 2001;48:27–42. https://doi.org/10.1016/S0169-409X(01)00098-9.

  6. Sandhu H, Shah N, Chokshi H, Malick AW. Overview of amorphous solid dispersion technologies. Amorphous solid dispersions: theory and practice. Springer, New York. 2014;91–122.

  7. He Y, Ho C. Amorphous solid dispersions: utilization and challenges in drug discovery and development. J Pharm Sci. 2015;104(10):3237–58. https://doi.org/10.1002/jps.24541.

    Article  CAS  PubMed  Google Scholar 

  8. Démuth B, et al. Downstream processing of polymer-based amorphous solid dispersions to generate tablet formulations. Int J Pharm. 2015;486(1–2):268–86. https://doi.org/10.1016/j.ijpharm.2015.03.053.

    Article  CAS  PubMed  Google Scholar 

  9. Madureira AR, Pereira CI, Gomes AM, Pintado ME, Malcata FX. Bovine whey proteins-Overview on their main biological properties. Food Res. 2007;40:1197–1211. https://doi.org/10.1016/j.foodres.2007.07.005.

  10. Morr CV, Ha EYW. Whey protein concentrates and isolates: processing and functional properties. Crit Rev Food Sci Nutr. 1993;33(6):431–76. https://doi.org/10.1080/10408399309527643.

  11. Farooq MA, et al. Whey protein: a functional and promising material for drug delivery systems recent developments and future prospects. Polym Adv Technol. 2019;30(9):2183–91. https://doi.org/10.1002/pat.4676.

    Article  CAS  Google Scholar 

  12. Liu W, Chen XD, Cheng Z, Selomulya C. On enhancing the solubility of curcumin by microencapsulation in whey protein isolate via spray drying. J Food Eng. 2016;169:189–95. https://doi.org/10.1016/j.jfoodeng.2015.08.034.

    Article  CAS  Google Scholar 

  13. MaHam, A, Tang, Z, Wu H, Wang J, Lin Y. Protein‐based nanomedicine platforms for drug delivery. Small. 2009;5(15):1706–21. https://doi.org/10.1002/smll.200801602.

  14. Li M, Ma Y, Cui J. Whey-protein-stabilized nanoemulsions as a potential delivery system for water-insoluble curcumin. LWT Food Sci Technol. 2014;59(1):49–58. https://doi.org/10.1016/j.lwt.2014.04.054.

    Article  CAS  Google Scholar 

  15. Allahdad Z, Varidi M, Zadmard R, Saboury AA, Haertlé T. Binding of β-carotene to whey proteins: Multi-spectroscopic techniques and docking studies. Food Chem. 2019;277(May 2018):96–106. https://doi.org/10.1016/j.foodchem.2018.10.057.

  16. Mishra J, Bohr A, Rades T, Grohganz H, Löbmann K. Whey proteins as stabilizers in amorphous solid dispersions. Eur J Pharm Sci. 2019;128(November 2018):144–151. https://doi.org/10.1016/j.ejps.2018.12.002.

  17. Bates S, Zografi G, Engers D, Morris K, Crowley K, Newman A. Analysis of amorphous and nanocrystalline solids from their X-ray diffraction patterns. Pharm Res. 2006;23(10):2333–49. https://doi.org/10.1007/s11095-006-9086-2.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Arla Foods Ingredients Group P/S for providing the samples of Lacprodan® BLG Pharma Grade, alpha-lactalbumin and Lacprodan® CGMP-20 and whey protein isolate.

Author information

Authors and Affiliations

  1. Zerion Pharma A/S, Fruebjergvej 3, 2100, Copenhagen, Denmark

    Donglei Leng, Bulut Bulduk, Ole Wiborg & Korbinian Löbmann

  2. Science for Novartis Pharma AG, Lichtstrasse 35, Ch-4002, Basel, Switzerland

    Toni Widmer & Manuel Sanchez-Felix

Authors
  1. Donglei Leng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bulut Bulduk
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Toni Widmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ole Wiborg
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Manuel Sanchez-Felix
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Korbinian Löbmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Korbinian Löbmann.

Ethics declarations

Conflict of Interest

Donglei Leng, Bulut Bulduk, Ole Wiborg and Korbinian Löbmann are employees at Zerion Pharma A/S, who is developing a technology based on the subject matter or materials discussed in this manuscript.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Leng, D., Bulduk, B., Widmer, T. et al. Protein Based Amorphous Solid Dispersion: a Case Study Investigating Different Whey Proteins at High Drug Loading. Pharm Res 40, 1865–1872 (2023). https://doi.org/10.1007/s11095-023-03542-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-023-03542-9

Keywords

Search

Navigation