Skip to main content
SpringerLink
Log in

Enhanced Dissolution and Stability of Lansoprazole by Cyclodextrin Inclusion Complexation: Preparation, Characterization, and Molecular Modeling

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

In this study, lansoprazole (LSP)/cyclodextrin (CD) inclusion complexes were prepared using a fluid bed coating technique, with β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (HPCD) as the host molecules, respectively, to simultaneously improve the dissolution and stability of LSP. The dissolution rate and stability of LSP was dramatically enhanced by inclusion complexation regardless of CD type. LSP/HPCD inclusion complex was more stable under illumination than LSP/β-CD inclusion complex. Differential scanning calorimetry and powder X-ray diffractometry proved the absence of crystallinity in both LSP/CD inclusion complexes. Fourier transform infrared spectroscopy together with molecular modeling indicated that the benzimidazole of LSP was included in the cavity of both CDs, while LSP was more deeply included in HPCD than β-CD. The enhanced photostability was due to the inclusion of the sulfinyl moiety into the HPCD cavity. CD inclusion complexation could improve the dissolution and stability of LSP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Gerloff J, Mignot A, Barth H, Heintze K. Pharmacokinetics and absolute bioavailability of lansoprazole. Eur J Clin Pharmacol. 1996;50:293–7.

    Article  PubMed  CAS  Google Scholar 

  2. Lew EA. Review article: pharmacokinetic concerns in the selection of anti-ulcer therapy. Aliment Pharmacol Ther. 1999;13 Suppl 5:11–6.

    Article  PubMed  CAS  Google Scholar 

  3. Stedman CA, Barclay ML. Review article: comparison of the pharmacokinetics, acid suppression and efficacy of proton pump inhibitors. Aliment Pharmacol Ther. 2000;14:963–78.

    Article  PubMed  CAS  Google Scholar 

  4. Sohn DR, Kwon JT, Kim HK, Ishizaki T. Metabolic disposition of lansoprazole in relation to the S-mephenytoin 4′-hydroxylation phenotype status. Clin Pharmacol Ther. 1997;61:574–82.

    Article  PubMed  CAS  Google Scholar 

  5. Pearce RE, Rodrigues AD, Goldstein JA, Parkinson A. Identification of the human P450 enzymes involved in lansoprazole metabolism. J Pharmacol Exp Ther. 1996;277:805–16.

    PubMed  CAS  Google Scholar 

  6. Ito Y, Arai H, Uchino K, Iwasaki K, Shibata N, Takada K. Effect of adsorbents on the absorption of lansoprazole with surfactant. Int J Pharm. 2005;289:69–77.

    Article  PubMed  CAS  Google Scholar 

  7. DellaGreca M, Iesce MR, Previtera L, Rubino M, Temussi F, Brigante M. Degradation of lansoprazole and omeprazole in the aquatic environment. Chemosphere. 2006;63:1087–93.

    Article  PubMed  CAS  Google Scholar 

  8. Zhang XW, Sun NY, Wu BJ, Lu Y, Guan TZ, Wu W. Physical characterization of lansoprazole/PVP solid dispersion prepared by fluid-bed coating technique. Powder Technol. 2008;182:480–5.

    Article  CAS  Google Scholar 

  9. Stroyer A, McGinity JW, Leopold CS. Solid state interactions between the proton pump inhibitor omeprazole and various enteric coating polymers. J Pharm Sci. 2006;95:1342–53.

    Article  PubMed  CAS  Google Scholar 

  10. Davis ME, Brewster ME. Cyclodextrin-based pharmaceutics: past, present and future. Nat Rev Drug Discov. 2004;3:1023–35.

    Article  PubMed  CAS  Google Scholar 

  11. Del Valle EMM. Cyclodextrins and their uses: a review. Process Biochem. 2004;39:1033–46.

    Article  Google Scholar 

  12. Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J Pharm Sci. 1996;85:1017–25.

    Article  PubMed  CAS  Google Scholar 

  13. Brewster ME, Loftsson T. Cyclodextrins as pharmaceutical solubilizers. Adv Drug Deliv Rev. 2007;59:645–66.

    Article  PubMed  CAS  Google Scholar 

  14. Loftsson T, Duchene D. Cyclodextrins and their pharmaceutical applications. Int J Pharm. 2007;329:1–11.

    Article  PubMed  CAS  Google Scholar 

  15. Ventura CA, Giannone I, Paolino D, Pistara V, Corsaro A, Puglisi G. Preparation of celecoxib-dimethyl-β-cyclodextrin inclusion complex: characterization and in vitro permeation study. Eur J Med Chem. 2005;40:624–31.

    Article  PubMed  CAS  Google Scholar 

  16. Kang J, Kumar V, Yang D, Chowdhury PR, Hohl RJ. Cyclodextrin complexation: influence on the solubility, stability, and cytotoxicity of camptothecin, an antineoplastic agent. Eur J Pharm Sci. 2002;15:163–70.

    Article  PubMed  CAS  Google Scholar 

  17. Figueiras A, Sarraguca JM, Carvalho RA, Pais AA, Veiga FJ. Interaction of omeprazole with a methylated derivative of β-cyclodextrin: phase solubility, NMR spectroscopy and molecular simulation. Pharm Res. 2007;24:377–89.

    Article  PubMed  CAS  Google Scholar 

  18. Lu Y, Zhang XW, Lai J, Yin ZN, Wu W. Physical characterization of meloxicam-β-cyclodextrin inclusion complex pellets prepared by a fluid-bed coating method. Particuology. 2009;7:1–8.

    Article  Google Scholar 

  19. Zhang XW, Wu DN, Lai J, Lu Y, Yin ZN, Wu W. Piroxicam/2-hydroxypropyl-β-cyclodextrin inclusion complex prepared by a new fluid-bed coating technique. J Pharm Sci. 2009;98:665–75.

    Article  PubMed  CAS  Google Scholar 

  20. Sun NY, Wei XL, Wu BJ, Chen J, Lu Y, Wu W. Enhanced dissolution of silymarin/polyvinylpyrrolidone solid dispersion pellets prepared by a one-step fluid-bed coating technique. Powder Technol. 2008;182:72–80.

    Article  CAS  Google Scholar 

  21. Manunza B, Deiana S, Pintore M, Gessa C. Structure and internal motion of solvated β-cyclodextrine: a molecular dynamics study. J Mol Struct. 1997;419:133–7.

    CAS  Google Scholar 

  22. Starikov EB, Brasicke K, Knapp EW, Saenger W. Negative solubility coefficient of methylated cyclodextrins in water: a theoretical study. Chem Phys Lett. 2001;336:504–10.

    Article  CAS  Google Scholar 

  23. Lawtrakul L, Viernstein H, Wolschann P. Molecular dynamics simulations of β-cyclodextrin in aqueous solution. Int J Pharm. 2003;256:33–41.

    Article  PubMed  CAS  Google Scholar 

  24. Jursic BS, Zdravkovski Z, French AD. Molecular modeling methodology of β-cyclodextrin inclusion complexes. J Mol Struct. 1996;366:113–7.

    CAS  Google Scholar 

  25. Alvira E, Mayoral JA, Garcia JI. Molecular modelling study of β-cyclodextrin inclusion complexes. Chem Phys Lett. 1997;271:178–84.

    Article  CAS  Google Scholar 

  26. Faucci MT, Melani F, Mura P. Computer-aided molecular modeling techniques for predicting the stability of drug-cyclodextrin inclusion complexes in aqueous solutions. Chem Phys Lett. 2002;358:383–90.

    Article  CAS  Google Scholar 

  27. Chen W, Chang CE, Gilson MK. Calculation of cyclodextrin binding affinities: energy, entropy, and implications for drug design. Biophys J. 2004;87:3035–49.

    Article  PubMed  CAS  Google Scholar 

  28. Lu Y, Tang N, Qi JP, Wu W. Phase solubility behavior of hydrophilic polymer/cyclodextrin/lansoprazole ternary system studied at high polymer concentration and by response surface methodology. Pharm Dev Technol. 2012;17:236–41.

    Article  PubMed  CAS  Google Scholar 

  29. Mura P, Bettinetti G, Melani F, Manderioli A. Interaction between naproxen and chemically modified β-cyclodextrins in the liquid and solid state. Eur J Pharm Sci. 1995;3:347–55.

    Article  CAS  Google Scholar 

  30. Madrid JM, Villafruela M, Serrano R, Mendicuti F. Experimental thermodynamics and molecular mechanics calculations of inclusion complexes of 9-methyl anthracenoate and 1-methyl pyrenoate with β-cyclodextrin. J Phys Chem B. 1999;103:4847–53.

    Article  CAS  Google Scholar 

  31. Ghorab MM, Abdel-Salam HM, El-Sayad MA, Mekhel MM. Tablet formulation containing meloxicam and β-cyclodextrin: mechanical characterization and bioavailability evaluation. AAPS PharmSciTech. 2004;5:e59.

    Article  PubMed  Google Scholar 

  32. Montassier P, Duchene D, Poelman MC. Inclusion complexes of tretinoin with cyclodextrins. Int J Pharm. 1997;153:199–209.

    Article  CAS  Google Scholar 

  33. Das S, Malik S, Jain B, Saini S. Synthesis and physicochemical studies of copper complex of lansoprazole. Orient J Chem. 2009;25:1129–31.

    CAS  Google Scholar 

  34. He W, Yang M, Fan JH, Feng CX, Zhang SJ, Wang JX, et al. Influences of sodium carbonate on physicochemical properties of lansoprazole in designed multiple coating pellets. AAPS PharmSciTech. 2010;11:1287–93.

    Article  PubMed  CAS  Google Scholar 

  35. Riel MA, Kyle DE, Bhattacharjee AK, Milhous WK. Efficacy of proton pump inhibitor drugs against Plasmodium falciparum in vitro and their probable pharmacophores. Antimicrob Agents Chemother. 2002;46:2627–32.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the Shanghai Commission of Education (10SG05) and the Shanghai Commission of Science and Technology (10430709200), the International Science and Technology Cooperation Project (S2010GR0920), and the Key National Science & Technology Projects (2010ZX09401-402).

Author information

Authors and Affiliations

  1. School of Pharmacy, Key Laboratory of Smart Drug Delivery of Ministry of Education and PLA, Fudan University, Shanghai, 201203, China

    Yi Lu, Jianping Qi & Wei Wu

  2. Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, State Key Laboratory of Drug Research, Chinese Academy of Sciences, Shanghai, 201203, China

    Tao Guo & Jiwen Zhang

  3. State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China

    Jiwen Zhang

Authors
  1. Yi Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tao Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jianping Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiwen Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wei Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jiwen Zhang or Wei Wu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lu, Y., Guo, T., Qi, J. et al. Enhanced Dissolution and Stability of Lansoprazole by Cyclodextrin Inclusion Complexation: Preparation, Characterization, and Molecular Modeling. AAPS PharmSciTech 13, 1222–1229 (2012). https://doi.org/10.1208/s12249-012-9842-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-012-9842-z

KEY WORDS

Search

Navigation