Skip to main content
SpringerLink
Log in

Molecular Weight Effects on the Miscibility Behavior of Dextran and Maltodextrin with Poly(vinylpyrrolidone)

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

To characterize and interpret the miscibility of dextran and maltodextrin with poly(vinylpyrrolidone) (DEX-PVP) as a function of polymer molecular weights.

Methods

Blend miscibility was studied using 4 different molecular weight (MW) grades of DEX combined with 5 MW grades of PVP, over a broad compositional range. Miscibility was evaluated by inspection of glass transition events measured by differential scanning calorimetry (DSC). Fourier transform mid-infrared spectroscopy (FTIR), combined with curve fitting, was performed to characterize the extent of hydrogen bonding. The observed miscibility behavior was further interpreted in terms of mixing thermodynamics.

Results

Miscibility of the blends ranged from fully miscible to completely immiscible with multiple partially miscible systems observed. Increasing polymer molecular weight decreased miscibility. For the lowest DEX grade, hydrogen bonding was independent of PVP MW, as expected since all systems were completely miscible. Higher molecular weights of DEX resulted in reduced intermolecular hydrogen bonding and decreased miscibility, increasingly so for higher MW PVP grades. Evaluation of the mixing thermodynamics supported these findings.

Conclusions

With higher combined molecular weights of DEX-PVP blends, phase behavior evolves from completely miscible to virtually immiscible. Concurrently, DEX-PVP hydrogen bonding decreases. From a thermodynamic perspective, the combinatorial mixing entropy was observed to decrease as the molecular weight of the polymers increased, providing a reduced counterbalance to the unfavorable mixing enthalpy thought to accompany this polymer combination.

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
Fig. 8

Similar content being viewed by others

References

  1. Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm. 2000;50(1):47–60.

    Article  PubMed  CAS  Google Scholar 

  2. Van Eerdenbrugh B, Taylor LS. Small scale screening to determine the ability of different polymers to inhibit drug crystallization upon rapid solvent evaporation. Mol Pharmaceutics. 2010;7(4):1328–37.

    Article  Google Scholar 

  3. Van Eerdenbrugh B, Taylor LS. An ab initio polymer selection methodology to prevent crystallization in amorphous solid dispersions by application of crystal engineering principles. CrystEngComm. 2011;13(20):6171–78.

    Google Scholar 

  4. Baird JA, Taylor LS. Evaluation of amorphous solid dispersion properties using thermal analysis techniques. Adv Drug Delivery Rev. doi:10.1016/j.addr.2011.07.009.

  5. Randolph TW. Phase separation of excipients during lyophilization: effects on protein stability. J Pharm Sci. 1997;86(1):1198–203.

    Article  PubMed  CAS  Google Scholar 

  6. Utracki LA. Glass transition temperature in polymer blends. Adv Polym Technol. 1985;5:33–9.

    Article  Google Scholar 

  7. Newman A, Engers D, Bates S, Ivanisevic I, Kelly RC, Zografi G. Characterization of amorphous API:polymer mixtures using X-ray powder diffraction. J Pharm Sci. 2008;97:4840–56.

    Article  PubMed  CAS  Google Scholar 

  8. Rumondor ACF, Marsac PJ, Stanford LA, Taylor LS. Phase behavior of poly(vinylpyrrolidone) containing amorphous solid dispersions in the presence of moisture. Mol Pharmaceutics. 2009;6(5):1492–505.

    Article  CAS  Google Scholar 

  9. Marsac PJ, Rumondor ACF, Nivens DE, Kestur US, Stanciu L, Taylor LS. Effect of temperature and moisture on the miscibility of amorphous dispersions of felodipine and poly(vinyl pyrrolidone). J Pharm Sci. 2010;99(1):169–85.

    Article  PubMed  CAS  Google Scholar 

  10. Rumondor ACF, Ivanisevic I, Bates S, Alonzo DE, Taylor LS. Evaluation of drug-polymer miscibility in amorphous solid dispersion systems. Pharm Res. 2009;26(11):2523–34.

    Article  PubMed  CAS  Google Scholar 

  11. Ivanisevic I, Bates S, Chen P. Novel methods for the assessment of miscibility of amorphous drug-polymer dispersions. J Pharm Sci. 2009;98(9):3373–86.

    Article  PubMed  CAS  Google Scholar 

  12. Padilla AM, Ivanisevic I, Yang YL, Engers D, Bogner RH, Pikal MJ. The study of phase separation in amorphous freeze-dried systems. part I: Raman mapping and computational analysis of XRPD data in model polymer systems. J Pharm Sci. 2011;100(1):206–22.

    Article  PubMed  CAS  Google Scholar 

  13. Qi S, Belton P, Nollenberger K, Clayden N, Reading M, Craig DQM. Characterisation and prediction of phase separation in hot-melt extruded solid dispersions: a thermal, microscopic and NMR relaxometry study. Pharm Res. 2010;27(9):1869–83.

    Article  PubMed  CAS  Google Scholar 

  14. Aso Y, Yoshioka S, Miyazaki T, Kawanishi T, Tanaka K, Kitamura S, Takakura A, Hayashi T, Muranushi N. Miscibility of nifedipine and hydrophilic polymers as measured by H-1-NMR spin-lattice relaxation. Chem Pharm Bull. 2007;55(8):1227–31.

    Article  PubMed  CAS  Google Scholar 

  15. Pham TN, Watson SA, Edwards AJ, Chavda M, Clawson JS, Strohmeier M, Vogt FG. Analysis of amorphous solid dispersions using 2D solid-state NMR and 1H T1 relaxation measurements. Mol Pharmaceutics. 2010;7(5):1667–91.

    Article  CAS  Google Scholar 

  16. Lauer ME, Grassmann O, Siam M, Tardio J, Jacob L, Page S, Kindt JH, Engel A, Alsenz J. Atomic force microscopy-based screening of drug-excipient miscibility and stability of solid dispersions. Pharm Res. 2011;28(3):572–84.

    Article  PubMed  CAS  Google Scholar 

  17. Padilla AM, Pikal MJ. The study of phase separation in amorphous freeze-dried systems, part 2: investigation of Raman mapping as a tool for studying amorphous phase separation in freeze-dried protein formulations. J Pharm Sci. 2011;100(4):1467–74.

    Article  CAS  Google Scholar 

  18. Padilla AM, Chou SG, Luthra S, Pikal MJ. The study of amorphous phase separation in a model polymer phase-separating system using Raman microscopy and a low-temperature stage: effect of cooling rate and nucleation temperature. J Pharm Sci. 2011;100(4):1362–76.

    Article  CAS  Google Scholar 

  19. Qi S, Belton P, Nollenberger K, Gryckze A, Craig DQM. Compositional analysis of low quantities of phase separation in hot-melt-extruded solid dispersions: a combined atomic force microscopy, photothermal Fourier-transform infrared microspectroscopy, and localised thermal analysis approach. Pharm Res. 2011;28(9):2311–26.

    Article  PubMed  CAS  Google Scholar 

  20. Six K, Murphy J, Weuts I, Craig DQM, Verreck G, Peeters J, Brewster M, Van den Mooter G. Identification of phase separation in solid dispersions of itraconazole and Eudragit® E100 using microthermal analysis. Pharm Res. 2003;20(1):135–8.

    Article  PubMed  CAS  Google Scholar 

  21. Galop M. Study of pharmaceutical solid dispersions by microthermal analysis. Pharm Res. 2005;22(2):293–302.

    Article  PubMed  CAS  Google Scholar 

  22. Zhang J, Bunker M, Parker A, Madden-Smith CE, Patel N, Roberts CJ. The stability of solid dispersions of felodipine in polyvinylpyrrolidone characterized by nanothermal analysis. Int J Pharm. 2011;414(1–2):210–7.

    Article  PubMed  CAS  Google Scholar 

  23. Van Eerdenbrugh B, Taylor LS. Application of mid-IR spectroscopy for the characterization of pharmaceutical systems. Int J Pharm. 2011;417(1–2):3–16.

    Article  PubMed  Google Scholar 

  24. Van Eerdenbrugh B, Lo M, Kjoller K, Marcott C, Taylor LS. Nanoscale Mid-Infrared Imaging of Phase Separation in a Drug-Polymer Blend. J Pharm Sci. Submitted.

  25. Izutsu K, Heller MC, Randolph TW, Carpenter JF. Effect of salts and sugars on phase separation of polyvinylpyrrolidone-dextran solutions induced by freeze-concentration. J Chem Soc, Faraday Trans. 1998;94(3):411–7.

    Article  CAS  Google Scholar 

  26. Izutsu K, Aoyagi N, Kojima S. Effect of polymer size and cosolutes on phase separation of poly(vinylpyrrolidone) (PVP) and dextran in frozen solutions. 2005;94(4):709–717.

  27. Izutsu K, Fujii K, Katori C, Yomota C, Kawanishi T, Yoshihashi Y, Yonemochi E, Terada K. Effects of solute miscibility on the micro- and macroscopic structural integrity of freeze-dried solids. J Pharm Sci. 2010;99(11):4710–9.

    Article  PubMed  CAS  Google Scholar 

  28. Shamblin SL, Taylor LS, Zografi G. Mixing behavior of colyophilized binary systems. J Pharm Sci. 1998;87(6):694–701.

    Article  PubMed  CAS  Google Scholar 

  29. Taylor LS, Zografi G. Sugar-polymer hydrogen bonding interactions in lyophilized amorphous mixtures. J Pharm Sci. 1998;87(2):1615–21.

    Article  PubMed  CAS  Google Scholar 

  30. Patterson D, Robarb A. Thermodynamics of polymer mixing. Macromolecules. 1978;11(4):690–5.

    Article  CAS  Google Scholar 

  31. Janarthanan V, Thyagarajan G. Miscibility studies in blends of poly(N-vinyl pyrrolidone) and poly(methyl methacrylate) with epoxy-resin—a comparison. Polymer. 1992;33(17):3593–7.

    Article  CAS  Google Scholar 

  32. Zhu KJ, Liquin W, Ji W, Shilin Y. Study of the miscibility of poly(N-vinyl-2-pyrrolidone) with polystyrene[styrene-co-(4-hydroxystyrene)]. Macromol Chem Phys. 1994;195(6):1965–72.

    Article  CAS  Google Scholar 

  33. Ahn SB, Jeong HM. Phase behavior and hydrogen bonding in poly(ethylene-co-vinyl alcohol) poly(N-vinyl-2-pyrrolidone) blends. Korea Polym J. 1998;6(5):389–95.

    CAS  Google Scholar 

  34. Garton A. Some Observations on Kinetic and Steric Limitations to Specific Interactions in Miscible Polymer Blends. Polym Eng Sci. 1984;24(2):112–6.

    Article  CAS  Google Scholar 

  35. Rubinstein M, Colby RH. Polymer Physics. New York: Oxford University Press Inc.; 2003.

    Google Scholar 

  36. Young RJ, Lovell PA. Introduction to polymers. Cheltenham: Nelson Thornes; 1991.

    Google Scholar 

  37. Flory PJ. Principles of polymer chemistry. Ithaca: Cornell University Press; 1953.

    Google Scholar 

Download references

Acknowledgments & DISCLOSURES

The authors thank the National Science Foundation Engineering Research Center for Structured Organic Particulate Systems (NSF ERC-SOPS)(EEC-0540855) for financial support. Elisabeth M. Topp, Ph.D. and Andreas M. Sophocleous, Ph.D. are thanked for providing access to the lyophilizer and help with freeze-drying experiments, respectively. BVE is a Postdoctoral Researcher of the ‘Fonds voor Wetenschappelijk Onderzoek’, Flanders, Belgium.

Author information

Authors and Affiliations

  1. Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907, USA

    Bernard Van Eerdenbrugh & Lynne S. Taylor

  2. Laboratory for Pharmacotechnology and Biopharmacy, K.U. Leuven, Gasthuisberg O&N2, Herestraat 49, box 921, 3000, Leuven, Belgium

    Bernard Van Eerdenbrugh

Authors
  1. Bernard Van Eerdenbrugh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lynne S. Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lynne S. Taylor.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

ESM 1

(DOC 1.28 mb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Van Eerdenbrugh, B., Taylor, L.S. Molecular Weight Effects on the Miscibility Behavior of Dextran and Maltodextrin with Poly(vinylpyrrolidone). Pharm Res 29, 2754–2765 (2012). https://doi.org/10.1007/s11095-012-0689-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-012-0689-5

Key Words

Search

Navigation