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Freeze-drying revolution: unleashing the potential of lyophilization in advancing drug delivery systems

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Abstract

Lyophilization also known as freeze-drying is a technique that has been employed to enhance the long-term durability of nanoparticles (NPs) that are utilized for drug delivery applications. This method is used to prevent their instability in suspension. However, this dehydration process can cause stress to the NPs, which can be alleviated by the incorporation of excipients like cryoprotectants and lyoprotectants. Nevertheless, the freeze-drying of NPs is often based on empirical principles without considering the physical–chemical properties of the formulations and the engineering principles of freeze-drying. For this reason, it is crucial to optimize the formulations and the freeze-drying cycle to obtain a good lyophilizate and ensure the preservation of NPs stability. Moreover, proper characterization of the lyophilizate and NPs is of utmost importance in achieving these goals. This review aims to update the recent advancements, including innovative formulations and novel approaches, contributing to the progress in this field, to obtain the maximum stability of formulations. Additionally, we critically analyze the limitations of lyophilization and discuss potential future directions. It addresses the challenges faced by researchers and suggests avenues for further research to overcome these limitations. In conclusion, this review is a valuable contribution to the understanding of the parameters involved in the freeze-drying of NPs. It will definitely aid future studies in obtaining lyophilized NPs with good quality and enhanced drug delivery and therapeutic benefits.

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Abbreviations

NPs:

Nanoparticles

FZ:

Freezing

PD:

Primary drying

SD:

Secondary drying

USFDA:

United States Food and Drug Administration

QBD:

Quality by design

RA:

Risk assessment

DS:

Design space

PAT:

Process analytical technology

QTPP:

Quality target product profile

T g :

Glass transition temperature

T e :

Eutectic temperature

T c :

Collapse temperature

ICH:

International Conference on Harmonisation

GAMP:

Good automated manufacturing practice

CFR:

Code of federal regulations

CAGR:

Compound annual growth rate

TEM:

Transmission electron microscopy

R&D:

Research and development

IQF:

Individually quick-frozen

SLNs:

Solid lipid nanoparticles

PDI:

Polydispersity index

ZP:

Zeta potential

EE%:

Entrapment efficiency

TFFD:

Thin film freeze drying

SNEDDS:

Self-nanoemulsifying drug delivery system

DSC:

Differential scanning calorimetry

XRD:

X-ray diffraction

NMs:

Nanomicelles

QUE:

Quercetin

CUR:

Curcumin

CSA:

Cyclosporin A

MCFAs:

Medium-chain fatty acids

Vit. C:

Vitamin C

REOs:

Rosemary essential oils

NE:

Nanoemulsion

PLGA:

Poly (lactic-co-glycolic acid)

CNTs:

Carbon nanotubes

GNRs:

Gold nanorods

AChE:

Acetylcholinesterase

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Acknowledgements

The authors would like to thank the DST-SERB, Government of India, for providing us the research support. The authors of the present article would like to express their sincere gratitude to the Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi, and Birla Institute of Technology and Science (BITS PILANI), Pilani, Rajasthan, for their kind support.

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The authors gratefully acknowledge the Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Government of India (File no. EEQ/2022/000008), in the preparation of the review article.

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  1. Department of Pharmaceutics, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi, 110017, India

    Sanchit Arora, Dimple Dhawan, Prabhat Kumar Sahoo & Dalapathi Gugulothu

  2. Department of Pharmacy, Birla Institute of Technology and Science (BITS PILANI), Pilani, Rajasthan, 333031, India

    Sanat Kumar Dash & Anil Jindal

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Arora, S., Dash, S.K., Dhawan, D. et al. Freeze-drying revolution: unleashing the potential of lyophilization in advancing drug delivery systems. Drug Deliv. and Transl. Res. 14, 1111–1153 (2024). https://doi.org/10.1007/s13346-023-01477-7

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