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LU Yan, CONG Feng, QIAN Shuai, WEI Yuanfeng, ZHANG Jianjun, LIN Yining, GAO Yuan. Enhanced dissolution and eliminated gelation of lenvatinib mesylate by coamorphous system[J]. Journal of China Pharmaceutical University, 2021, 52(1): 44-51. DOI: 10.11665/j.issn.1000-5048.20210106
Citation: LU Yan, CONG Feng, QIAN Shuai, WEI Yuanfeng, ZHANG Jianjun, LIN Yining, GAO Yuan. Enhanced dissolution and eliminated gelation of lenvatinib mesylate by coamorphous system[J]. Journal of China Pharmaceutical University, 2021, 52(1): 44-51. DOI: 10.11665/j.issn.1000-5048.20210106
shu

Enhanced dissolution and eliminated gelation of lenvatinib mesylate by coamorphous system

  • 1.

    School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198

  • 2.

    School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China

Funds: This study was supported by the National Natural Science Foundation of China (No.81703712, No.81773675, No.81873012) and the Double First-Class Project of China Pharmaceutical University (No.CPU2018GY11, No.CPU2018GY27)
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  • Received Date: August 09, 2020
  • Revised Date: December 07, 2020
    Graphical Abstract
    • Abstract
  • Lenvatinib mesylate (LF), a multi-target tyrosinase inhibitor mainly used in the treatment of a variety of cancers, has low oral bioavailability mainly due to its gelation during the dissolution process. In the current study, in order to enhance dissolution and eliminate gelation of LF, a supramolecular coamorphous system of LF-baicalein (BAI) (molar ratio, 1∶1) was prepared by rotary evaporation and characterized by PLM, PXRD, DSC and FTIR. Results indicated the formation of coamorphous system with a single Tg of 118 °C. Different from original LF crystal, no gelation phenomenon was observed during the dissolution of coamorphous LF-BAI. In addition, the dissolution rate of LF was increased by 2.2-fold after coamorphization. Meanwhile, the dissolution rate of the co-former BAI was also enhanced by more than 25.4-fold. Stability test showed that the prepared coamorphous system had a good physical stability for at least 90 days under 25 °C/ 60%RH and 40 °C /75%RH conditions.
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    • References (21)
  • [1]
    . Drug Discov Today， 2012， 17（9/10）： 486-495.
    [2]
    Shi Q， Moinuddin SM， Cai T. Advances in coamorphous drug delivery systems［J］. Acta Pharm Sin B， 2019， 9（1）： 19-35.
    [3]
    Lu WD， Rades T， Rantanen J， et al. Inhalable co-amorphous budesonide-arginine dry powders prepared by spray drying［J］. Int J Pharm， 2019， 565： 1-8.
    [4]
    Moinuddin SM， Ruan SD， Huang YT， et al. Facile formation of co-amorphous atenolol and hydrochlorothiazide mixtures via cryogenic-milling：enhanced physical stability，dissolution and pharmacokinetic profile［J］. Int J Pharm， 2017， 532（1）： 393-400.
    [5]
    Guo HH，Miao NN，Li TF，et al．Pharmaceutical coamorphous：a newly defined single-phase amorphous binary system［J］．Prog Chem（化学进展），2014，26（2/3）：478-486．
    [6]
    Qian S，Heng WL，Wei YF，et al．Coamorphous lurasidone Hydrochloride-saccharin with charge-assisted hydrogen bonding interaction shows improved physical stability and enhanced dissolution with pH-independent solubility behavior［J］．Cryst Growth Des，2015，15（6）：2920-2928．
    [7]
    Qian S，Li Z，Heng WL，et al．Charge-assisted intermolecular hydrogen bond formed in coamorphous system is important to relieve the pH-dependent solubility behavior of lurasidone hydrochloride［J］．RSC Adv，2016，6（108）：106396-106412．
    [8]
    Bao XJ，Chen X，Wang SR，et al．Coamorphous combinations of poorly water-soluble drugs dabigatran etexilate mesylate and tadalafil for improving dissolution and physical stability［J］．J China Pharm Univ （中国药科大学学报），2019，50（5）：549-559．
    [9]
    Qian S， Wang SS， Li Z， et al. Charge-assisted bond N+H mediates the gelation of amorphous lurasidone hydrochloride during dissolution［J］. Int J Pharm， 2017， 518（1/2）： 335-341.
    [10]
    Heng WL， Su ML， Cheng H， et al. Incorporation of complexation into a coamorphous system dramatically enhances dissolution and eliminates gelation of amorphous lurasidone hydrochloride［J］. Mol Pharm， 2020， 17（1）： 84-97.
    [11]
    Hong DS， Kurzrock R， Falchook GS， et al. Phase 1b study of lenvatinib （E7080） in combination with temozolomide for treatment of advanced melanoma［J］. Oncotarget， 2015， 6（40）： 43127-43134.
    [12]
    Matsui J， Funahashi Y， Uenaka T， et al. Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor （VEGF-R） 2 and VEGF-R3 kinase［J］. Clin Cancer Res， 2008， 14（17）： 5459-5465.
    [13]
    Molina AM， Hutson TE， Larkin J， et al. A phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib （E7080） in combination with everolimus for treatment of metastatic renal cell carcinoma （RCC）［J］. Cancer Chemother Pharmacol， 2014， 73（1）： 181-189.
    [14]
    Ikeda M， Okusaka T， Mitsunaga S， et al. Safety and pharmacokinetics of lenvatinib in patients with advanced hepatocellular carcinoma［J］. Clin Cancer Res， 2016， 22（6）： 1385-1394.
    [15]
    Schlumberger M， Tahara M， Wirth LJ， et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer［J］. N Engl J Med， 2015， 372（7）： 621-630.
    [16]
    Lorusso L， Newbold K. Lenvatinib： a new option for the treatment of advanced iodine refractory differentiated thyroid cancer［J］？Future Oncol， 2015， 11（12）： 1719-1727.
    [17]
    Wang L， Ling Y， Chen Y， et al. Flavonoid baicalein suppresses adhesion， migration and invasion of MDA-MB-231 human breast cancer cells［J］. Cancer Lett， 2010， 297（1）： 42-48.
    [18]
    Motoo Y， Sawabu N. Antitumor effects of saikosaponins， baicalin and baicalein on human hepatoma cell lines［J］. Cancer Lett， 1994， 86（1）： 91-95.
    [19]
    Huang YT， Zhang BW， Gao Y， et al. Baicalein-nicotinamide cocrystal with enhanced solubility， dissolution， and oral bioavailability［J］. J Pharm Sci， 2014， 103（8）： 2330-2337.
    [20]
    L?bmann K， Flouda K， Qiu DW， et al. The influence of pressure on the intrinsic dissolution rate of amorphous indomethacin［J］. Pharmaceutics， 2014， 6（3）： 481-493.
    [21]
    Liu ML，Liang XT，Iinuma M，et al．The structure of rehderianin I， a correction［J］．Acta Pharm Sin （药学学报），1986，21（9）：706-707．
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