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Nanosuspensions of 10-hydroxycamptothecin that can maintain high and extended supersaturation to enhance oral absorption: preparation, characterization and in vitro/in vivo evaluation

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Abstract

The purpose of the study was to prepare and characterize nanosuspensions that can maintain high and extended supersaturation to improve the dissolution and absorption of poorly soluble 10-hydroxycamptothecin (10-HCPT). 10-HCPT oral nanosuspensions (HCPT-Nanosuspensions) were produced on a laboratory-scale by microprecipitation- high pressure homogenization method. The particle morphology and the physical state were studied using transmission electron microscopy, X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC). Supersaturated dissolution tests were carried out with the paddle method. Caco-2 cell experiments were performed to imitate the oral absorption. The in vivo pharmacokinetics studies were undertaken in rats following oral administration. The 10-HCPT nanoparticles were 135 nm in dimension before lyophilization and were claviform or lump in shape. XRPD and DSC both confirmed that a portion of 10-HCPT was present in a crystalline state in nanosuspension. Supersaturated dissolution tests showed HCPT-Nanosuspensions could maintain high supersaturated level for an extended period time. The cell experiment on HCPT-Nanosuspensions showed a significantly higher uptake and greater membrane permeability compared with the other formulations. The pharmacokinetic test exhibited HCPT-Nanosuspensions had a similar pharmacokinetic performance with 10-HCPT solution. In conclusion, highly and extendedly supersaturated HCPT-Nanosuspensions have been prepared which could result in high peak concentration (C max) and great exposure (AUC) after oral administration.

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Acknowledgments

The authors would like to acknowledge the support of this study by the National Natural Science Foundation of China (NSFC), No. 81173008 and the National Basic Research Program of China (973 program, 2009CB930300).

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Authors and Affiliations

  1. Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, No. 59 Mailbox, Shenyang, 110016, China

    Xiaohui Pu, Jin Sun, He Lian, Peng Zhang & Zhonggui He

  2. Department of Pharmaceutical Analysis, School of Pharmacy, Henan University, Jinming Road, Kaifeng, 475004, China

    Xiaohui Pu

  3. School of Pharmacy and Institute for Science and Technology in Medicine, Keele University, Staffordshire, UK

    Jihong Han

  4. Nantion Institutes for Food and Drug Control, No. 2, Tiantan Xili, Beijing, 100050, China

    Zhongtian Yan

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  1. Xiaohui Pu
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  2. Jin Sun
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  3. Jihong Han
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  4. He Lian
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  5. Peng Zhang
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  6. Zhongtian Yan
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  7. Zhonggui He
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Correspondence to Jin Sun or Zhonggui He.

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Pu, X., Sun, J., Han, J. et al. Nanosuspensions of 10-hydroxycamptothecin that can maintain high and extended supersaturation to enhance oral absorption: preparation, characterization and in vitro/in vivo evaluation. J Nanopart Res 15, 2043 (2013). https://doi.org/10.1007/s11051-013-2043-1

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  • DOI: https://doi.org/10.1007/s11051-013-2043-1

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