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Spray-Dried Microspheres of Carboplatin: Technology to Develop Longer-Acting Injectable with Improved Physio-Chemical Stability, Toxicity, and Therapeutics

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Abstract

The present study aims to develop carboplatin injectable microspheres using spray-drying technology. The optimized powdered microspheres (MS-19-ST2) were morphologically spherical, with a 1.795 μm particle size and good micromeritic properties. Under normal temperature conditions, the MS-19-ST2 formulation exhibited a sustained release behaviour following first-order drug release kinetics with no compatibility issues with aluminium syringes. Furthermore, MS-19-ST2 formulation outperformed its commercial counterpart in terms of in vivo pharmaco-kinetics and -dynamics (MRT-13.9 ± 0.9 h, T1/2–8.2 ± 0.3 h, tumour inhibition-74.5%). Additionally, the MS-19-ST2 formulation was much safer to use than its commercial counterpart, as observed from the results of ex vivo (haemolytic, MTT, and cell apoptosis assays) and in vivo (14-day acute and 28-day sub-acute) toxicity studies. The above results confirm the MS-19-ST2 formulation as a good candidate to commercialize carboplatin in a powdered microsphere form (stable for 24 h after reconstitution) with improved pharmacokinetics, therapeutic, and toxicity profile.

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Acknowledgments

This project was supported by the University Grants Commission (UGC) under RUSA 2.0 Component 4 Scheme provided to Guru Nanak Dev University, Amritsar (Prof. (Dr.) Subheet Kumar Jain, Principal-Investigator). We are also thankful for providing a grant under the DST-FIST scheme to the Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India

    Shubham Thakur & Subheet Kumar Jain

  2. Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, 143005, India

    Rasdeep Kour & Satwinderjeet Kaur

  3. Centre for Basic and Translational Research in Health Sciences, Guru Nanak Dev University, Amritsar, 143005, India

    Subheet Kumar Jain

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  1. Shubham Thakur
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  2. Rasdeep Kour
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Contributions

Shubham Thakur contributed to conceptualization, methodology, investigation, validation, formal analysis, writing—original draft, visualization; Rasdeep Kaur contributed to methodology, investigation, validation, formal analysis; Satwinderjeet Kaur contributed to conceptualization, supervision, writing—review and editing; Subheet Kumar Jain contributed to conceptualization, supervision, writing—review and editing.

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Correspondence to Subheet Kumar Jain.

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Thakur, S., Kour, R., Kaur, S. et al. Spray-Dried Microspheres of Carboplatin: Technology to Develop Longer-Acting Injectable with Improved Physio-Chemical Stability, Toxicity, and Therapeutics. AAPS PharmSciTech 23, 128 (2022). https://doi.org/10.1208/s12249-022-02281-1

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