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Microwave-Assisted Development of Orally Disintegrating Tablets by Direct Compression

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ABSTRACT

Orally disintegrating tablets (ODTs) are challenged by the need for simple technology to ensure good mechanical strength coupled with rapid disintegration. The objective of this work was to evaluate microwave-assisted development of ODTs based on simple direct compression tableting technology. Placebo ODTs comprising directly compressible mannitol and lactose as diluents, super disintegrants, and lubricants were prepared by direct compression followed by exposure to >97% relative humidity and then microwave irradiation for 5 min at 490 W. Placebo ODTs with hardness (>5 kg/cm2) and disintegration time (<60 s) were optimized. Palatable ODTs of Lamotrigine (LMG), which exhibited rapid dissolution of LMG, were then developed. The stability of LMG to microwave irradiation (MWI) was confirmed. Solubilization was achieved by complexation with beta-cyclodextrin (β-CD). LMG ODTs with optimal hardness and disintegration time (DT) were optimized by a 23 factorial design using Design Expert software. Taste masking using sweeteners and flavors was confirmed using a potentiometric multisensor-based electronic tongue, coupled with principal component analysis. Placebo ODTs with crospovidone as a superdisintegrant revealed a significant increase in hardness from ∼3 to ∼5 kg/cm2 and a decrease in disintegration time (<60 s) following microwave irradiation. LMG ODTs had hardness >5 kg/cm2, DT < 30s, and rapid dissolution of LMG, and good stability was optimized by DOE and the design space derived. While β-CD complexation enabled rapid dissolution and moderate taste masking, palatability, which was achieved including flavors, was confirmed using an electronic tongue. A simple step of humidification enabled MWI-facilitated development of ODTs by direct compression presenting a practical and scalable advancement in ODT technology.

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Acknowledgements

The authors are thankful to the University Grants Commission, Government of India, Department of Science & Technology (DST), Government of India and Russian Foundation for Basic Research (grant INT/RUS/RFBR/P-195 and RFBR no. 15-53-45105), and DST Prime Ministers Fellowship for financial support. Dmitry Kirsanov and Andrey Legin acknowledge partial financial support from Government of Russian Federation (grant 074-U01).

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Deemed University, Elite Status and Centre of Excellence (Maharashtra), N.P. Marg, Matunga (E), Mumbai, 400019, Maharashtra, India

    Kishor V. Kande, Darsheen J. Kotak, Mariam S. Degani & Padma V. Devarajan

  2. Institute of Chemistry, St. Petersburg State University, Universitetskaya nab. 7/9, Mendeleev Center, 199034, St. Petersburg, Russia

    Dmitry Kirsanov & Andrey Legin

  3. Laboratory of Artificial Sensory Systems, ITMO University, Kronverkskiy pr., 49, 197101, St. Petersburg, Russia

    Dmitry Kirsanov & Andrey Legin

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  1. Kishor V. Kande
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  2. Darsheen J. Kotak
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  3. Mariam S. Degani
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  4. Dmitry Kirsanov
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  6. Padma V. Devarajan
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Correspondence to Padma V. Devarajan.

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Kande, K.V., Kotak, D.J., Degani, M.S. et al. Microwave-Assisted Development of Orally Disintegrating Tablets by Direct Compression. AAPS PharmSciTech 18, 2055–2066 (2017). https://doi.org/10.1208/s12249-016-0683-z

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  • DOI: https://doi.org/10.1208/s12249-016-0683-z

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