Skip to main content

Molecular Motions in Sucrose-PVP and Sucrose-Sorbitol Dispersions: I. Implications of Global and Local Mobility on Stability

Pharmaceutical Research volume 28, pages 2191–2203 (2011)Cite this article

ABSTRACT

Purpose

To characterize molecular mobility by dielectric spectroscopy and determine the effect of additives on α- and β-relaxation times in amorphous sucrose solid dispersions.

Methods

Sucrose was co-lyophilized with either PVP or sorbitol. The lyophiles were subjected to dielectric spectroscopy and differential scanning calorimetry.

Results

The additives did not have an appreciable effect on the calorimetric Tg. However, dielectric spectroscopy revealed pronounced effects on global mobility (α-relaxation), which correlated with the crystallization tendency of sucrose. The systems were characterized by two β-relaxations, and the relaxation times as well as their temperature dependence were influenced by the additive. Although sorbitol acted as a plasticizer of sucrose with respect to global mobility, it anti-plasticized sucrose in terms of local motions. PVP, on the other hand, acted as an anti-plasticizer with respect to both global and local mobility. The slower β-relaxation in amorphous sucrose was found to correlate with the α-relaxation and was identified as the Johari-Goldstein relaxation.

Conclusions

Amorphous systems with identical calorimetric Tg could have significantly different mobility and physical stability as revealed by dielectric spectroscopy. Additive effect on global mobility cannot be a predictor of the effects on local mobility. Additives could also be used to inhibit local mobility.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

REFERENCES

  1. Pouton CW. Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci. 2006;29:278–87.

    PubMed  Article  CAS  Google Scholar 

  2. Bhugra C, Rambhatla S, Bakri A, Duddu SP, Miller DP, Pikal MJ, et al. Prediction of the onset of crystallization of amorphous sucrose below the calorimetric glass transition temperature from correlations with mobility. J Pharm Sci. 2007;96:1258–69.

    PubMed  Article  CAS  Google Scholar 

  3. Bhugra C, Shmeis RA, Krill SL, Pikal MJ. Predictions of onset of crystallization from experimental relaxation times I-Correlation of molecular mobility from temperatures above the glass transition to temperatures below the glass transition. Pharm Res. 2006;23:2277–90.

    PubMed  Article  CAS  Google Scholar 

  4. Bhugra C, Shmeis RA, Krill SL, Pikal MJ. Prediction of onset of crystallization from experimental relaxation times. II. Comparison between predicted and experimental onset times. J Pharm Sci. 2008;97:455–72.

    PubMed  Article  CAS  Google Scholar 

  5. Shamblin SL, Hancock BC, Pikal MJ. Coupling between chemical reactivity and structural relaxation in pharmaceutical glasses. Pharm Res. 2006;23:2254–68.

    PubMed  Article  CAS  Google Scholar 

  6. Shamblin SL, Tang X, Chang L, Hancock BC, Pikal MJ. Characterization of the time scales of molecular motion in pharmaceutically important glasses. J Phys Chem B. 1999;103:4113–21.

    Article  CAS  Google Scholar 

  7. Craig DQM, Royall PG, Kett VL, Hopton ML. The relevance of the amorphous state to pharmaceutical dosage forms: glassy drugs and freeze-dried systems. Int J Pharm. 1999;179:179–207.

    PubMed  Article  CAS  Google Scholar 

  8. Yu L. Amorphous pharmaceutical solids: preparation, characterization and stabilization. Adv Drug Deliv Rev. 2001;48:27–42.

    PubMed  Article  CAS  Google Scholar 

  9. Kerc J, Srcic S. Thermal analysis of glassy pharmaceuticals. Thermochim Acta. 1995;248:81–95.

    Article  CAS  Google Scholar 

  10. Hilden LR, Morris KR. Physics of amorphous solids. J Pharm Sci. 2001;93:3–12.

    Article  Google Scholar 

  11. Vyazovkin S, Dranca I. Effect of physical aging on nucleation of amorphous indomethacin. J Phys Chem B. 2007;111:7283–7.

    PubMed  Article  CAS  Google Scholar 

  12. Yoshioka S, Miyazaki T, Aso Y. β-relaxation of insulin molecule in lyophilized formulations containing trehalose or dextran as a determinant of chemical reactivity. Pharm Res. 2006;23:961–6.

    PubMed  Article  CAS  Google Scholar 

  13. Yoshioka S, Miyazaki T, Aso Y, Kawanishi T. Significance of local mobility in aggregation of β-galactosidase lyophilized with trehalose, sucrose or stachyose. Pharm Res. 2007;24:1660–7.

    PubMed  Article  CAS  Google Scholar 

  14. Alie J, Menegotto J, Cardon P, Duplaa H, Caron A, Lacabanne C, et al. Dielectric study of the molecular mobility and the isothermal crystallization kinetics of an amorphous pharmaceutical drug substance. J Pharm Sci. 2004;93:218–33.

    PubMed  Article  CAS  Google Scholar 

  15. Hikima T, Adachi Y, Hanaya M, Oguni M. Determination of potentially homogeneous-nucleation-based crystallization in o-terphenyl and an interpretation of the nucleation-enhancement mechanism. Phys Rev B Condens Matter. 1995;52:3900–8.

    PubMed  Article  CAS  Google Scholar 

  16. Hikima T, Hanaya M, Oguni M. Discovery of a potentially homogeneous-nucleation-based crystallization around the glass transition temperature in salol. Solid State Commun. 1995;93:713–7.

    Article  CAS  Google Scholar 

  17. Hikima T, Hanaya M, Oguni M. Microscopic observation of a peculiar crystallization in the glass transition region and β-process as potentially controlling the growth rate in triphenylethylene. J Mol Struct. 1999;479:245–50.

    Article  CAS  Google Scholar 

  18. Hikima T, Okamoto N, Hanaya M, Oguni M. Calorimetric study of triphenylethene: observation of homogeneous-nucleation-based crystallization. J Chem Thermodyn. 1998;30:509–23.

    Article  CAS  Google Scholar 

  19. Sixou B, Faivre A, David L, Vigier G. Intermolecular and intramolecular contributions to the relaxation process in sorbitol and maltitol. Mol Phys. 2001;99:1845–50.

    Article  CAS  Google Scholar 

  20. Gusseme AD, Carpentier L, Willart JF, Descamps M. Molecular mobility in supercooled trehalose. J Phys Chem B. 2003;107:10879–86.

    Article  Google Scholar 

  21. Johari GP. Intrinsic mobility of molecular glasses. J Chem Phys. 1973;58:1766–70.

    Article  CAS  Google Scholar 

  22. Johari GP, Goldstein M. Viscous liquids and the glass transition. II. Secondary relaxations in glasses of rigid molecules. J Chem Phys. 1970:2372–2388.

  23. Ngai KL. An extended coupling model description of the evolution of dynamics with time in supercooled liquids and ionic conductors. J Phys Condens Matter. 2003;15:S1107–25.

    Article  CAS  Google Scholar 

  24. Hancock BC, Shamblin SL, Zografi G. Molecular mobility of amorphous pharmaceutical solids below their glass transition temperatures. Pharm Res. 1995;12:799–806.

    PubMed  Article  CAS  Google Scholar 

  25. Vyazovkin S, Dranca I. Probing beta relaxation in pharmaceutically relevant glasses by using DSC. Pharm Res. 2006;23:422–8.

    PubMed  Article  CAS  Google Scholar 

  26. Zeng XM, Martin GP, Marriott C. Effects of molecular weight of polyvinylpyrrolidone on the glass transition and crystallization of co-lyophilized sucrose. Int J Pharm. 2001;218:63–73.

    PubMed  Article  CAS  Google Scholar 

  27. Shamblin SL, Huang EY, Zografi G. The effects of co-lyophilized polymeric additives on the glass transition temperature and crystallization of amorphous sucrose. J Therm Anal. 1996;47:1567–79.

    Article  CAS  Google Scholar 

  28. Shamblin SL, Zografi G. The effects of absrobed water on the properties of amorphous mixtures containing sucrose. Pharm Res. 1999;16:1119–24.

    PubMed  Article  CAS  Google Scholar 

  29. Johari GP, Kim S, Shanker RM. Dielectric studies of molecular motions in amorphous solid and ultraviscous acetaminophen. J Pharm Sci. 2005;94:2207–23.

    PubMed  Article  CAS  Google Scholar 

  30. Crowley KJ, Zografi G. The use of thermal methods for predicting glass-former fragility. Thermochim Acta. 2001;380:79–93.

    Article  CAS  Google Scholar 

  31. Kremer F. Dielectric spectroscopy—yesterday, today and tomorrow. J Non-Cryst Solids. 2002;305:1–9.

    Article  CAS  Google Scholar 

  32. Kremer F, Schonhals A, editors. Broadband dielectric spectroscopy. Berlin: Springer; 2003.

    Google Scholar 

  33. Craig DQM. Dielectric analysis of pharmaceutical systems. London: Taylor & Francis; 1995.

    Google Scholar 

  34. Hancock BC, Zografi G. Characteristics and significance of the amorphous state in pharmaceutical systems. J Pharm Sci. 1997;86:1–12.

    PubMed  Article  CAS  Google Scholar 

  35. Alig I, Braun D, Langendorf R, Voigt M, Wendorff JH. Simultaneous aging and crystallization processes within the glassy state of a low molecular weight substance. J Non-Cryst Solids. 1997;221:261–4.

    Article  CAS  Google Scholar 

  36. Grzybowska K, Pawlus S, Mierzwa M, Paluch M, Ngai KL. Changes of relaxation dynamics of a hydrogen-bonded glass former after removal of the hydrogen bonds. J Chem Phys. 2006;125:144507/1–8.

    CAS  Google Scholar 

  37. Kaminski K, Kaminska E, Hensel-Bielowka E, Chelmecka E, Paluch M, Ziolo J, et al. Identification of the molecular motions responsible for the slower secondary (β) relaxation in sucrose. J Phys Chem B. 2008;112:7662–8.

    PubMed  Article  CAS  Google Scholar 

  38. Vanhal I, Blond G. Impact of melting conditions of sucrose on its glass transition temperature. J Agr Food Chem. 1999;47:4285–90.

    Article  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  40. Ediger MD, Harrowell P, Yu L. Crystal growth kinetics exhibit a fragility-dependent decoupling from viscosity. J Chem Phys. 2008;128:034709/1–6.

    Article  CAS  Google Scholar 

  41. Sun Y, Xi H, Ediger MD, Yu L. Diffusionless crystal growth from glass has precursor in equilibrium liquid. J Phys Chem B. 2008;112:661–4.

    PubMed  Article  CAS  Google Scholar 

  42. Kudlik A, Benkhof S, Blochowicz T, Tschirwitz C, Rossler E. The dielectric response of simple organic glass formers. J Mol Struct. 1999;479:201–18.

    Article  CAS  Google Scholar 

  43. Ngai KL, Capaccioli S. Relation between the activation energy of the Johari-Goldstein β relaxation and Tg of glass formers. Phys Rev E. 2004;69:031501/1–5.

    Article  CAS  Google Scholar 

  44. Kaminski K, Kaminska E, Paluch M, Ziolo J, Ngai KL. The true Johari-Goldstein β-relaxation of monosaccharides. J Phys Chem B. 2006;110:25045–9.

    PubMed  Article  CAS  Google Scholar 

  45. Noel TR, Ring SG, Whittam MA. Dielectric relaxations of small carbohydrate molecules in the liquid and glassy states. J Phys Chem. 1992;96:5662–7.

    Article  CAS  Google Scholar 

  46. Noel TR, Parker R, Ring SG. Effect of molecular structure and water content on the dielectric relaxation behavior of amorphous low molecular weight carbohydrates above and below their glass transition. Carbohydr Res. 2000;329:839–45.

    PubMed  Article  CAS  Google Scholar 

  47. Surana R, Pyne A, Suryanarayanan R. Effect of preparation method on physical properties of amorphous trehalose. Pharm Res. 2004;21:1167–76.

    PubMed  Article  CAS  Google Scholar 

  48. Johari GP. Effect of annealing on the secondary relaxations in glasses. J Chem Phys. 1982;77:4619–26.

    Article  CAS  Google Scholar 

  49. Ngai KL, Paluch M. Classification of secondary relaxation in glass-formers based on dynamic properties. J Chem Phys. 2004;120:857–73.

    PubMed  Article  CAS  Google Scholar 

  50. Cicerone MT, Soles CL. Fast dynamics and stabilization of proteins: binary glasses of trehalose and glycerol. Biophys J. 2004;86:3836–45.

    PubMed  Article  CAS  Google Scholar 

  51. Cicerone MT, Tellington A, Trost L, Sokolov A. Substantially improved stability of biological agents in dried form. BioProcess Int. 2003;1:36–47.

    CAS  Google Scholar 

  52. Duddu SP, Sokoloski TD. Dielectric analysis in the characterization of amorphous pharmaceutical solids. 1. Molecular mobility in poly(vinylpyrrolidone)-water systems in the glassy state. J Pharm Sci. 1995;84:773–6.

    PubMed  Article  CAS  Google Scholar 

  53. Nozaki R, Suzuki D, Ozawa S, Shiozaki Y. The α and the β relaxation processes in supercooled sorbitol. J Non-Cryst Solids. 1998;235–237:393–8.

    Article  Google Scholar 

  54. Jain SK, Johari GP. Dielectric studies of molecular motions in the glassy states of pure and aqueous poly(vinylpyrrolidone). J Phys Chem. 1988;92:5851–4.

    Article  CAS  Google Scholar 

  55. Taylor LS, Zografi G. Sugar-polymer hydrogen bond interactions in lyophilized amorphous mixtures. J Pharm Sci. 1998;87:1615–21.

    PubMed  Article  CAS  Google Scholar 

  56. Colmenero J, Arbe A, Alegria A. Crossover from Debye to non-Debye dynamical behavior of the α relaxation observed by quasielastic neutron scattering in a glass-forming polymer. Phys Rev Lett. 1993;71:2603–6.

    PubMed  Article  CAS  Google Scholar 

  57. Colmenero J, Arbe A, Alegria A. The dynamics of the α- and β-relaxations in glass-forming polymers studied by quasielastic neutron scattering and dielectric spectroscopy. J Non-Cryst Solids. 1994;172–174:126–37.

    Article  Google Scholar 

  58. Ngai KL. Relation between some secondary relaxations and the α relaxations in glass-forming materials according to the coupling model. J Chem Phys. 1998;109:6982–94.

    Article  CAS  Google Scholar 

  59. Alvarez F, Alegria A, Colmenero J. Relationship between the time-domain Kohlrausch-Williams-Watts and frequency-domain Havriliak-Negami relaxation functions. Phys Rev B Condens Matter. 1991;44:7306–12.

    PubMed  Article  Google Scholar 

Download references

ACKNOWLEDGMENTS

We thank Brad Givot (3M, St. Paul, MN) for all his help, support and insightful comments during the course of the project, and 3M (St. Paul, MN) for providing us generous access to the dielectric spectrometer. Sunny Bhardwaj is thanked for his comments.

Author information

Author notes

  1. Sisir Bhattacharya

    Present address: Forest Research Institute, Forest Laboratories, Inc., 49 Mall Drive, Commack, New York, 11725, USA

Affiliations

  1. Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, 55455, USA

    Sisir Bhattacharya & Raj Suryanarayanan

Authors
  1. Sisir Bhattacharya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raj Suryanarayanan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Raj Suryanarayanan.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bhattacharya, S., Suryanarayanan, R. Molecular Motions in Sucrose-PVP and Sucrose-Sorbitol Dispersions: I. Implications of Global and Local Mobility on Stability. Pharm Res 28, 2191–2203 (2011). https://doi.org/10.1007/s11095-011-0447-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-011-0447-0

KEY WORDS

  • amorphous
  • dielectric spectroscopy
  • global and local mobility
  • solid dispersions
  • sucrose