Preparation and Evaluation of Probucol-Phospholipid Complex with Enhanced Bioavailability and No Food Effect

Abstract

To enhance the oral bioavailability and eliminate the food effect of probucol. Probucol-phospholipid complex was prepared using solvent-evaporation method in this research. Several methods were used to validate the formation of complexes, such as FT-IR, SEM, DSC and PXRD, and the solubility of PRO and PRO-PLC was detected by HPLC. Pharmacokinetic testing was conducted in the fasted and fed state. FTIR, SEM, DSC and PXRD validated the existence of PRO-PLC. The solubility of PRO in complexes was 15.05 μg/mL, which was 215-fold of the PRO-API. The dissolution rate was increased by preparing PRO-PLC. Compared with commercial tablets, the PRO-PLC complexes exhibited higher peak plasma concentration (1.69 ± 0.44 μg/mL), increased AUC0–24 h (6.8 ± 1.3 μg/mL h), which mean the bioavailability of PRO was increased. In addition, the absorption of PRO was not interfered with food. In conclusion, an improved solubility and bioavailability was achieved with the preparation of PRO-PLC. Additionally, the dissolution behaviour was good and the food effect was eliminated.

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Correspondence to Lili Ren.

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Guest Editor: Sanyog Jain

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Qian, Y., Chen, G., Wang, J. et al. Preparation and Evaluation of Probucol-Phospholipid Complex with Enhanced Bioavailability and No Food Effect. AAPS PharmSciTech 19, 3599–3608 (2018). https://doi.org/10.1208/s12249-018-1157-2

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KEY WORDS

  • solubility
  • bioavailability
  • food effect
  • phospholipid complex
  • probucol