AAPS PharmSciTech

, Volume 19, Issue 8, pp 3599–3608 | Cite as

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

  • Yiwen Qian
  • Guoguang Chen
  • Jin Wang
  • Lili RenEmail author
Research Article Theme: Lipid-Based Drug Delivery Strategies for Oral Drug Delivery
Part of the following topical collections:
  1. Theme: Lipid-Based Drug Delivery Strategies for Oral Drug Delivery


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.


solubility bioavailability food effect phospholipid complex probucol 


  1. 1.
    Kubo Y, Terashima Y, Yagi N, Nochi H, Tamoto K, Sekikawa H. Enhanced bioavailability of probucol following the administration of solid dispersion systems of probucol-polyvinylpyrrolidone in rabbits. Biol Pharm Bull. 2009;32:1880–4.CrossRefPubMedGoogle Scholar
  2. 2.
    Shudo J, Pongpeerapat A, Wanawongthai C, Moribe K, Yamamoto K. In vivo assessment of oral administration of probucol nanoparticles in rats. Biol Pharm Bull. 2008;31:321–5.CrossRefPubMedGoogle Scholar
  3. 3.
    Russell JC, Graham SE, Amy RM, Dolphin PJ. Cardioprotective effect of probucol in the atherosclerosis-prone JCR LA-cp rat. Eur J Pharmacol. 1998;350:203–10.CrossRefPubMedGoogle Scholar
  4. 4.
    Zaitseva TM, Lupanov VP, Lyakishev AA, Titov VN, Polevaya TY. Pharmacokinetics of probucol dosage forms in clinical tests. Pharma Chem. 1995;29:21–3.Google Scholar
  5. 5.
    Heeg JF, Hiser MF, Satonin DK, Rose JQ. Pharmacokinetics of probucol in male rats. J Pharm Sci. 1984;73:1758–63.CrossRefPubMedGoogle Scholar
  6. 6.
    Io T, Fukami T, Yamamoto K, Suzuki T, Xu JD, Tomono K. Homogeneous nanoparticles to enhance the efficiency of ahydrophobic drug anti-hyperlipidemic probucol characterized by solid-state NMR. Mol Pharm. 2009;7:1–12.Google Scholar
  7. 7.
    Nielsen FS, Petersen KB, Mullertz A. Bioavailability of probucol from lipid and surfactant based formulations in minipigs: influence of droplet size and dietary state. Eur J Pharm Biopharm. 2008;69:553–62.CrossRefPubMedGoogle Scholar
  8. 8.
    Xianyi S, Juan W, Yanzuo C, Xiaoling F. Self-microemulsifying drug delivery system for improved oral bioavailability of probucol: preparation and evaluation. Int J Nanomedicine. 2012;7:705–12.CrossRefGoogle Scholar
  9. 9.
    Miao Y, Chen G, Ren L. Preparation and evaluation of ziprasidone-phospholipid complex from sustained-release pellet formulation with enhanced bioavailability and no food effect. J Pharm Pharmacol. 2016;68(2):185–94.CrossRefPubMedGoogle Scholar
  10. 10.
    Singh C. Novel rifampicinphospholipid complex for tubercular therapy: synthesis, physicochemical characterization and in-vivo evaluation. Int J Pharm. 2014;460:220–7.CrossRefGoogle Scholar
  11. 11.
    Gupta NK. Bioavailability enhancement of curcumin by complexation with phosphatidylcholine. J Pharm Sci. 2011;100:1987–95.CrossRefPubMedGoogle Scholar
  12. 12.
    Yu JN. Enhancement of oral bioavailability of the poorly water soluble drug silybin by sodium cholate/phospholipid-mixed micelles. Acta Pharmacol Sin. 2010;31:759–64.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Hequn M. Improving permeability and oral absorption of mangiferin by phospholipid complexation. Fitoterapia. 2014;93:54–61.CrossRefGoogle Scholar
  14. 14.
    Khan J, Alexander A, Ajazuddin Saraf S, Saraf S. Recent advances and future prospects of phyto-phospholipid complexation technique for improving pharmacokinetic profile of plant actives. J Control Release. 2013;168:50–60.CrossRefGoogle Scholar
  15. 15.
    Afanaseva YG, Fakhretdinova ER, Spirikhin LV, Nasibullin RS. Mechanism of interaction of certain flavonoids with phosphatidylcholine of cellular membranes. Pharm Chem J. 2007;41:354–6.CrossRefGoogle Scholar
  16. 16.
    Mezghrani O, Ke X, Bourkaib N, Xu BH. Optimized self-microemulsifying drug delivery systems (SMEDDS) for enhanced oral bioavailability of astilbin. Pharmazie. 2011;66:754–60.PubMedGoogle Scholar
  17. 17.
    National Pharmacopoeia Commission. “Chinese Pharmacopoeia 2015” version II [S]. Beijing: China Medical Sci Technol Press; 2015. Appendix XI XC Guidelines for Stability Testing of APIs and Pharmaceutical Preparations.Google Scholar
  18. 18.
    Kim Y. Inclusion complexation of ziprasidone mesylate with beta-cyclodextrin sulfobutyl ether. J Pharm Sci. 1998;87:1560–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Bei G. Application of phospholipid complex technique to improve the dissolution and pharmacokinetic of probucol by solvent-evaporation and co-grinding methods. Int J Pharm. 2014;474:50–6.CrossRefGoogle Scholar
  20. 20.
    Jena SK. Development of tamoxifen-phospholipid complex: novel approach for improving solubility and bioavailability. Int J Pharm. 2014;473:1–9.CrossRefGoogle Scholar
  21. 21.
    Semalty A. Development and physicochemical evaluation of pharmacosomes of diclofenac. Acta Pharma. 2009;59:335–44.CrossRefGoogle Scholar
  22. 22.
    Yanyu X. The preparation of silybin phospholipid complex and the study on its pharmacokinetics in rats. Int J Pharm. 2006;307:7–82.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  1. 1.School of PharmacyNanjing Tech UniversityNanjingChina

Personalised recommendations