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Molecular mechanism of polymer-assisting supersaturation of poorly water-soluble loratadine based on experimental observations and molecular dynamic simulations

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Abstract

Polymers have been usually used to retard nucleation and crystal growth in order to maintain supersaturation, yet their roles in inhibition of nucleation and crystal growth are poorly understood. In our work, the polymer-based supersaturation performances and molecular mechanisms of poorly aqueous soluble loratadine were investigated. Two common hydrophilic polymers (hydroxylpropylmethyl cellulose acetate succinate (HPMC-AS) and poly(vinylpyrrolidone-co-vinyl-acetate) (PVP-VA)) were used. It was found that HPMC-AS was a better polymer to prevent drug molecules from aggregation and to maintain the supersaturated state in solution than PVP-VA. The in vitro dissolution experiments showed that HPMC-AS solid dispersions had more rapid release at pH 4.5 and 6.8 media than PVP-VA solid dispersions under the un-sink condition. Moreover, molecular dynamic simulation results showed that HPMC-AS was more firmly absorbed onto a surface of the drug nanoparticles than PVP-VA due to bigger hydrophobic areas of HPMC-AS. Thereby, crystallization process of loratadine was inhibited in the presence of water to provide prolonged stability of the supersaturated state. In conclusion, polymers played a key role in maintaining supersaturation state of loratadine solid dispersions by strong drug–polymer interactions and the hydrophobic characteristic of polymers.

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Acknowledgements

The authors report no declaration of interest. We thank financial support from the National Natural Science Foundation of China (No. 81473164, J1210029). We also thank financial support from Project for New Century Excellent Talents of Ministry of Education (No. NCET-12-1015). The research was financially supported by the Education Department of Liaoning Province (Grant LJQ2015109) and the Scientific Research Foundation for the Returned Overseas Scholars in Shenyang Pharmaceutical University (GGJJ2014101).

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Authors and Affiliations

  1. Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang, 110016, China

    Shenwu Zhang, Mengchi Sun, Zhonggui He & Jin Sun

  2. School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang, 110016, China

    Yongshan Zhao

  3. Department of Pharmaceutics, University of Florida, Gainesville, FL, 32610, USA

    Xuyang Song

  4. Key Laboratory of Structure-Based Drug Design and Discovery, Shenyang Pharmaceutical University, Ministry of Education, Wenhua Road, No. 103, Shenyang, 110016, China

    Jian Wang

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  1. Shenwu Zhang
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Correspondence to Jian Wang or Jin Sun.

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Zhang, S., Sun, M., Zhao, Y. et al. Molecular mechanism of polymer-assisting supersaturation of poorly water-soluble loratadine based on experimental observations and molecular dynamic simulations. Drug Deliv. and Transl. Res. 7, 738–749 (2017). https://doi.org/10.1007/s13346-017-0401-8

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  • DOI: https://doi.org/10.1007/s13346-017-0401-8

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