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Application of the QbD Approach in the Development of a Liposomal Formulation with EGCG

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Abstract

Purpose

The aim of this study was to develop liposomes loaded with (-)- epigallocatechin gallate (EGCG) by using the Quality by Design (QbD) approach.

Methods

The risk assessment tools (Ishikawa diagram and Risk Estimation Matrix) highlighted three formulation factors, namely phospholipid concentration, phospholipid to cholesterol molar ratio and EGCG concentration that are likely to influence the critical quality attributes (CQAs) of the EGCG containing liposomes and thus were studied through a D-optimal experimental design.

Results

The results revealed that all three formulation factors presented a great influence on liposomes CQAs. High concentrations of EGCG and cholesterol were observed to increase the encapsulation of EGCG into liposomes at low values of the phospholipid concentration. On the other hand, high concentrations of EGCG increased liposomal size and zeta potential values. The optimal formulation featured an entrapped drug concentration of 221.9 µg/ml, corresponding to an encapsulation efficiency of 69.2%, while the liposomal size was 175.2 nm. The release profile illustrated a prolonged release of EGCG from the optimal formulation on a period of 72 h, with a total percentage released of 56%. The in vitro studies performed on dental follicle (DF) mesenchymal stem cells and periodontal ligament (PDL) mesenchymal stem cells showed that EGCG exert its antioxidant effect on DF but not on PDL.

Conclusion

The application of the QbD concept in the development of EGCG loaded liposomes improved the understanding of the manufacturing process as well as the influence of the formulation factors on the quality attributes of liposomes.

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Funding

This research was financed by the University of Medicine and Pharmacy Iuliu Hațieganu Cluj-Napoca, Romania, under Grant no. 1529/7/18.01.2019 and under Grant no. 4944/16/8.03.2016.

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Authors and Affiliations

  1. Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, University of Medicine and Pharmacy “Iuliu Hațieganu”, Cluj-Napoca, Romania

    Cristina Ioana Barbălată, Ioan Tomuță, Marcela Achim & Alina Silvia Porfire

  2. Department of Histology, Faculty of Medicine, University of Medicine and Pharmacy “Iuliu Hațieganu”, Cluj-Napoca, Romania

    Adina Bianca Boșca

  3. Radiotherapy, Radiobiology and Tumor Biology Laboratory, “Ioan Chiricuță”, Cluj-Napoca, Romania

    Gabriela Cherecheș & Olga Sorițău

Authors
  1. Cristina Ioana Barbălată
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  2. Ioan Tomuță
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  3. Marcela Achim
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  4. Adina Bianca Boșca
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  5. Gabriela Cherecheș
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Correspondence to Ioan Tomuță.

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Barbălată, C.I., Tomuță, I., Achim, M. et al. Application of the QbD Approach in the Development of a Liposomal Formulation with EGCG. J Pharm Innov 17, 867–880 (2022). https://doi.org/10.1007/s12247-021-09541-w

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