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Liquid antisolvent crystallization of pharmaceutical compounds: current status and future perspectives

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Abstract

The present work reviews the liquid antisolvent crystallization (LASC) to prepare the nanoparticle of pharmaceutical compounds to enhance their solubility, dissolution rate, and bioavailability. The application of ultrasound and additives is discussed to prepare the particles with narrow size distribution. The use of ionic liquid as an alternative to conventional organic solvent is presented. Herbal compounds, also known for low aqueous solubility and limited clinical application, have been crystalized by LASC and discussed here. The particle characteristics such as particle size and particle size distribution are interpreted in terms of supersaturation, nucleation, and growth phenomena. To overcome the disadvantage of batch crystallization, the scientific literature on continuous flow reactors is also reviewed. LASC in a microfluidic device is emerging as a promising technique. The different design of the microfluidic device and their application in LASC are discussed. The combination of the LASC technique with traditional techniques such as high-pressure homogenization and spray drying is presented. A comparison of product characteristics prepared by LASC and the supercritical CO2 antisolvent method is discussed to show that LASC is an attractive and inexpensive alternative for nanoparticle preparation. One of the major strengths of this paper is a discussion on less-explored applications of LASC in pharmaceutical research to attract the attention of future researchers.

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Authors and Affiliations

  1. Department of Chemical Engineering, Energy Cluster, University of Petroleum and Energy Studies, Dehradun, 248007, Uttarakhand, India

    Rahul Kumar, Amit K. Thakur & Nilanjana Banerjee

  2. Department of Chemical Engineering, Indian Institute of Technology Delhi, 110016, New Delhi, India

    Ashutosh Kumar

  3. Sustainable Process Integration Laboratory, SPIL, NETME Centre, Faculty of Mechanical Engineering, Brno University of Technology, VUT Brno, Technická 2896/2, 616 69, Brno, Czech Republic

    Gajendra Kumar Gaurav

  4. Department of Chemical Engineering, Dr. B.R. Ambedkar National Institute of Technology, Jalandhar, India

    Raj Kumar Arya

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Contributions

Dr. Rahul Kumar took a lead in writing this manuscript. Dr. Amit K. Thakur wrote the nanonization of herbal drugs. Dr. Nilanjana Banerjee revised the section “Comparison of LASC and other techniques.” Dr. Ashutosh Kumar wrote the combinative approach. Dr. Gajendra Kumar Gaurav edited the original draft of manuscript. Dr. Nilanjana Banerjee and Dr. Raj Kumar Arya did editing of the revised version of the manuscript.

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Kumar, R., Thakur, A.K., Banerjee, N. et al. Liquid antisolvent crystallization of pharmaceutical compounds: current status and future perspectives. Drug Deliv. and Transl. Res. 13, 400–418 (2023). https://doi.org/10.1007/s13346-022-01219-1

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