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Design and Evaluation of a Novel Evodiamine-Phospholipid Complex for Improved Oral Bioavailability

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  • Theme: Advanced Technologies for Oral Controlled Release
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Abstract

A novel evodiamine (EVO)-phospholipid complex (EPLC) was designed to improve the bioavailability of EVO. A central composite design approach was employed for process optimization. EPLC were characterized by differential scanning calorimetry, ultraviolet spectroscopy, Fourier transformed infrared spectroscopy, 1H-NMR spectroscopy, matrix-assisted laser desorption/ionization time-of-flight spectroscopy, apparent solubility, and dissolution rate. After oral administration of EPLC, the concentrations of EVO at different time points were determined by high-performance liquid chromatography. The optimal formulation for EPLC was obtained where the values of X 1, X 2, and X 3 were 2, 0.5, and 2.5 mg/mL, respectively. The average particle size and zeta potential of EPLC with the optimized formulation were 246.1 nm and −26.94 mV, respectively. The EVO and phospholipids in the EPLC were associated with non-covalent interactions. The solubility of EPLC in water and the dissolution rate of EPLC in phosphate-buffered solution (pH 6.8) were substantially enhanced. The plasma EVO concentration-time curves of EPLC and free EVO were both in accordance with the two-compartment model. The peak concentration and AUC0−∞ of EPLC were increased, and the relative bioavailability was significantly increased to 218.82 % compared with that of EVO.

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ACKNOWLEDGMENTS

The authors wish to thank the National Natural Science Foundation of China (no. 30973645), Chongqing Natural Science Foundation (No. CSCT2012JJB10019), and Specialized Research Fund for the Doctoral Program of Higher Education (no. 20095503120008).

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Authors and Affiliations

  1. Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, People’s Republic of China

    Qunyou Tan

  2. Chongqing Key Laboratory of Biochemical and Molecular Pharmacology, Medicine Engineering Research Center, Chongqing Medical University, Chongqing, 400042, People’s Republic of China

    Shan Liu, Xueliang Chen, Mingjun Wu, Hong Wang, Huafeng Yin, Dan He, Huarong Xiong & Jingqing Zhang

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  1. Qunyou Tan
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  2. Shan Liu
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Correspondence to Jingqing Zhang.

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Guest Editors: Michael Repka, Joseph Reo, Linda Felton, and Stephen Howard

Shan Liu is co-first author.

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Tan, Q., Liu, S., Chen, X. et al. Design and Evaluation of a Novel Evodiamine-Phospholipid Complex for Improved Oral Bioavailability. AAPS PharmSciTech 13, 534–547 (2012). https://doi.org/10.1208/s12249-012-9772-9

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  • DOI: https://doi.org/10.1208/s12249-012-9772-9

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