Skip to main content
SpringerLink
Log in

Distribution and Effect of Water Content on Molecular Mobility in Poly(vinylpyrrolidone) Glasses: A Molecular Dynamics Simulation

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

Purpose

This work explores the distribution of water and its effects on molecular mobilities in poly(vinylpyrrolidone) (PVP) glasses using molecular dynamics (MD) simulation technology.

Methods

PVP glasses containing 0.5% and 10% w/w water and a small amount of ammonia and Phe-Asn-Gly were generated. Physical aging processes and associated structural and dynamic properties were monitored vs. time for periods up to 0.1 μs by MD simulation.

Results

Increasing water content from 0.5% to 10% w/w was found to reduce the Tg by about 90 K and increase the rates of volume and enthalpy relaxation. At 0.5% w/w, water molecules are mostly isolated and uniformly distributed while at 10% w/w, water distribution is markedly heterogeneous, with strands of water molecules occupying channels between the polymer chains. At 10% w/w, each water molecule has an average of 2.0 neighboring water molecules. The plasticization effects of water were revealed in diffusion coefficient increases of 3.7-, 7.3-, and 7.6-fold for water, ammonia, and the individual polyvinylpyrrolidone segments, respectively, and in shorter relaxation times (37- to 47-fold) for rotation of polymer segments with an elevation in water content from 0.5% to 10% w/w. Water diffusivity was found to linearly correlate with the number of neighboring water molecules. Rotation of the PVP segments is comprised of a fast wobble motion within a highly restrained cavity and a slow rotation over a wider angular space. Only the slow rotation was shown to be significantly affected by water content.

Conclusions

Water distribution in the PVP glass is highly heterogeneous at 10% w/w water, reflecting the formation of water strands or small clusters rather than complete phase separation. Local enhancement of mobility with increasing water content has been demonstrated using MD simulations.

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
Fig. 9

Similar content being viewed by others

Abbreviations

ACF:

autocorrelation function

DSC:

differential scanning calorimetry

ESP:

electrostatic potential

MD:

molecular dynamics

NMR:

nuclear magnetic resonance

PVP:

poly(vinylpyrrolidone)

References

  1. J. L. Ford (1986) ArticleTitleThe current status of solid dispersions Pharm. Acta Helv. 61 69–88 Occurrence Handle3520598

    PubMed  Google Scholar 

  2. B. C. Hancock M. Parks (2000) ArticleTitleWhat is the true solubility advantage of amorphous pharmaceuticals? Pharm. Res. 17 397–404 Occurrence Handle10.1023/A:1007516718048 Occurrence Handle10870982

    Article  PubMed  Google Scholar 

  3. K. Khougaz S.-D. Clas (2000) ArticleTitleCrystallization inhibition in solid dispersion of MK-0591 and poly(vinylpyrrolidone) polymers J. Pharm. Sci. 89 1325–1334 Occurrence Handle10.1002/1520-6017(200010)89:10<1325::AID-JPS10>3.0.CO;2-5 Occurrence Handle10980507

    Article  PubMed  Google Scholar 

  4. P. Gupta V. K. IKakumanu A. K. Bansal (2004) ArticleTitleStability and solubility of celecoxib-PVP amorphous dispersions: a molecular perspective Pharm. Res. 21 1762–1769 Occurrence Handle10.1023/B:PHAM.0000045226.42859.b8 Occurrence Handle15553220

    Article  PubMed  Google Scholar 

  5. Y. Aso S. Yoshioka S. Kojima (2004) ArticleTitleMolecular mobility-based estimation of the crystallization rates of amorphous nifedipine and phenobarbital in poly(vinylpyrrolidone) solid dispersions J. Pharm. Sci. 93 384–391 Occurrence Handle10.1002/jps.10526 Occurrence Handle14705195

    Article  PubMed  Google Scholar 

  6. N. Rodriguez-Hornedo D. Murphy (1999) ArticleTitleSignificance of controlling crystallization mechanism and kinetics in pharmaceutical systems J. Pharm. Sci. 88 651–660 Occurrence Handle10.1021/js980490h Occurrence Handle10393562

    Article  PubMed  Google Scholar 

  7. S. R. Byrn, R. R. Pfeiffer, and J. G. Stowell. Solid-State Chemistry of Drugs, SSCI, Inc., West Lafayette, IN, 1999.

  8. S. R. Byrn W. Xu A. W. Newman (2001) ArticleTitleChemical reactivity in solid-state pharmaceuticals: formulation implications Adv. Drug Deliv. Rev. 48 115–136 Occurrence Handle10.1016/S0169-409X(01)00102-8 Occurrence Handle11325479

    Article  PubMed  Google Scholar 

  9. J. E. Carpenter M. J. Pikal B. S. Chang T. W. Randolph (1997) ArticleTitleRational design of stable lyophilized protein formulations: some practical advice Pharm. Res. 14 969–975 Occurrence Handle10.1023/A:1012180707283 Occurrence Handle9279875

    Article  PubMed  Google Scholar 

  10. M. J. Hageman (1992) Water sorption and solid state stability of proteins T. J. Ahern M. C. Manning (Eds) Stability of Protein Pharmaceuticals: Chemical and Physical Pathways of Protein Degradation Plenum New York

    Google Scholar 

  11. B. C. Hancock S. L. Shamblin G. Zografi (1995) ArticleTitleMolecular mobility of amorphous pharmaceutical solids below their glass transition temperatures Pharm. Res. 12 799–806 Occurrence Handle10.1023/A:1016292416526 Occurrence Handle7667182

    Article  PubMed  Google Scholar 

  12. C. A. Oksanen G. Zografi (1993) ArticleTitleMolecular mobility in mixtures of absorbed water and solid poly(vinylpyrrolidone) Pharm. Res. 10 791–799 Occurrence Handle10.1023/A:1018988506336 Occurrence Handle8391695

    Article  PubMed  Google Scholar 

  13. S. Yoshioka Y. Aso K. Izutsu T. Terao (1993) ArticleTitleStability of β-galactosidase, a model protein drug, is related to water mobility as measured by 17O nuclear magnetic resonance (NMR) Pharm. Res. 10 103–108 Occurrence Handle10.1023/A:1018933315538 Occurrence Handle8430045

    Article  PubMed  Google Scholar 

  14. S. Yoshioka Y. Aso T. Otsuka S. Kojima (1995) ArticleTitleWater mobility in poly(ethylene glycol)-, poly(vinylpyrrolidone)-, and gelatin-water systems, as indicated by dielectric relaxation times, spin-lattice relaxation time, and water activity J. Pharm. Sci. 84 1072–1077 Occurrence Handle8537884

    PubMed  Google Scholar 

  15. S. Yoshioka Y. Aso S. Kojima S. Sakurai T. Fujiwara H. Akutsu (1999) ArticleTitleMolecular mobility of protein in lyophilized formulations linked to the molecular mobility of polymer excipients, as determined by high resolution 13C solid-state NMR Pharm. Res. 16 1621–1625 Occurrence Handle10.1023/A:1018973125010 Occurrence Handle10554107

    Article  PubMed  Google Scholar 

  16. S. Yoshioka Y. Aso S. Kojima (1999) ArticleTitleThe effect of excipients onthe molecular mobility of lyophilized formulations, as measured by glass transition temperature and NMR relaxation-based critical mobility temperature Pharm. Res. 16 135–140 Occurrence Handle10.1023/A:1018891317006 Occurrence Handle9950292

    Article  PubMed  Google Scholar 

  17. S. Bone (1987) ArticleTitleTime-domain reflectrometry studies of water binding and structural flexibility in chymotrypsin Biochim. Biophys. Acta 916 128–134 Occurrence Handle3663682

    PubMed  Google Scholar 

  18. S. P. Duddu T. D. Sokoloski (1995) ArticleTitleDielectric analysis in the characterization of amorphous pharmaceutical solids. 1. Molecular mobility in poly(vinylpyrrolidone)-water systems in the glassy state J. Pharm. Sci. 84 773–776 Occurrence Handle7562421

    PubMed  Google Scholar 

  19. M. Fukuda S. Kuwajima (1997) ArticleTitleMolecular-dynamics simulation of moisture diffusion in polyethylene beyond 10 ns duration J. Chem. Phys. 107 2149–2159 Occurrence Handle10.1063/1.474564

    Article  Google Scholar 

  20. G. E. Karlsson U. W. Gedde M. S. Hedenqvist (2004) ArticleTitleMolecular dynamics simulation of oxygen diffusion in dry and water-containing poly(vinyl alcohol) Polymer 45 3893–3900 Occurrence Handle10.1016/j.polymer.2003.12.082

    Article  Google Scholar 

  21. T.-X. Xiang B. D. Anderson (2004) ArticleTitleA molecular dynamics simulation of reactant mobility in an amorphous formulation of a peptide in poly(vinylpyrrolidone) J. Pharm. Sci. 93 855–876 Occurrence Handle10.1002/jps.20004 Occurrence Handle14999724

    Article  PubMed  Google Scholar 

  22. L. N. Bell M. J. Hageman J. M. Bauer (1995) ArticleTitleImpact of moistureon thermally induced denaturation and decomposition of lyophilized bovine somatotropin Biopolymers 35 201–209 Occurrence Handle10.1002/bip.360350208 Occurrence Handle7696565

    Article  PubMed  Google Scholar 

  23. L. N. Bell M. J. Hageman L. M. Muraoka (1995) ArticleTitleThermally induced denaturation of lyophilized bovine somatotropin and lysozyme as impacted by moisture and excipients J. Pharm. Sci. 84 707–712 Occurrence Handle7562408

    PubMed  Google Scholar 

  24. M. C. Lai M. J. Hageman R. L. Schowen R. T. Borchardt B. B. Laird E. M. Topp (1999) ArticleTitleChemical stability of peptides in polymers. 2. Discriminating between solvent and plasticizing effects of water on peptide deamidation in poly(vinyl pyrrolidone) J. Pharm. Sci. 88 1081–1089 Occurrence Handle10.1021/js9802289 Occurrence Handle10514359

    Article  PubMed  Google Scholar 

  25. L. N. Bell M. J. Hageman (1994) ArticleTitleDifferentiating between the effects of water activity and glass transition dependent mobility on a solid state chemical reaction: aspartame degradation J. Agric. Food Chem. 40 873–879

    Google Scholar 

  26. T. Hamaura J. M. Newton (1999) ArticleTitleInteraction between water and poly(vinylpyrrolidone) containing polyethylene glycol J. Pharm. Sci. 88 1228–1233 Occurrence Handle10.1021/js980354c Occurrence Handle10564074

    Article  PubMed  Google Scholar 

  27. B. C. Hancock G. Zografi (1994) ArticleTitleThe relationship between the glass transition temperature and the water content of amorphous pharmaceutical solids Pharm. Res. 11 471–477 Occurrence Handle10.1023/A:1018941810744 Occurrence Handle8058600

    Article  PubMed  Google Scholar 

  28. R. K. Bharadwaj R. H. Boyd (2000) ArticleTitleEffect of pressure on conformational dynamics in polyethylene: a molecular dynamics simulation study Macromolecules 33 5897–5905 Occurrence Handle10.1021/ma0004615

    Article  Google Scholar 

  29. O. Hahn D. A. Mooney F. Muller-Plathe K. Kremer (1999) ArticleTitleA new mechanism for penetrant diffusion in amorphous polymers:molecular dynamics simulations for phenol diffusion in bisphenol-A-polycarbonate J. Chem. Phys. 111 6061–6068 Occurrence Handle10.1063/1.479904

    Article  Google Scholar 

  30. B. F. Abu-Sharkh (2001) ArticleTitleGlass transition temperature of poly(vinylchloride) from molecular dynamics simulation: Explicit atom model versus rigid CH2 and CHCl groups model Comput. Theor. Polymer Sci. 11 29–34 Occurrence Handle10.1016/S1089-3156(99)00070-7

    Article  Google Scholar 

  31. S. U. Boyd R. H. Boyd (2001) ArticleTitleChain dynamics and relaxation in amorphous poly(ethylene terephthalate): a molecular dynamics simulation study Macromolecules 34 7219–7229 Occurrence Handle10.1021/ma0106797

    Article  Google Scholar 

  32. E. Tocci D. Hofmann D. Paul N. Russo E. Drioli (2001) ArticleTitleA molecular simulation study on gas diffusion in a dense poly(ether-ether-ketone) membrane Polymer 42 521–533 Occurrence Handle10.1016/S0032-3861(00)00102-6

    Article  Google Scholar 

  33. J. H. D. Boshoff R. F. Lobo N. J. Wagner (2001) ArticleTitleInfluence of polymer motion, topology and simulation size on penetrant diffusion in amorphous, glassy polymers: diffusion of helium in polypropylene Macromolecules 34 6107–6116 Occurrence Handle10.1021/ma010255c

    Article  Google Scholar 

  34. G. E. Karlsson T. S. Johansson U. W. Gedde M. S. Hedenqvist (2002) ArticleTitlePhysical properties of dense amorphous poly(vinyl alcohol) as revealed by molecular dynamics simulation J. Macromol. Sci., Phys. B41 185–206

    Google Scholar 

  35. A. P. Simonelli S. C. Mehta W. I. Higuchi (1970) ArticleTitleInhibition of sulfathiazole crystal growth by polyvinylpyrrolidone J. Pharm. Sci. 59 633–638 Occurrence Handle5446418

    PubMed  Google Scholar 

  36. H. Sekikawa M. Nakano T. Arita (1978) ArticleTitleInhibitory effect of polyvinylpyrrolidone on the crystallization of drugs Chem. Pharm. Bull. 26 118–126

    Google Scholar 

  37. M. Lai M. J. Hageman R. L. Schowen E. M. Topp (1999) ArticleTitleChemical stability of peptides in polymers. 1. Effect of water on peptide deamidation in poly(vinyl alcohol) and poly(vinylpyrrolidone) matrices J. Pharm. Sci. 10 1073–1080 Occurrence Handle10.1021/js980227g

    Article  Google Scholar 

  38. R. G. Strickley B. D. Anderson (1996) ArticleTitleSolid-state stability of human insulin I. Mechanism and the effect of water on the kinetics of degradation in lyophiles from pH 2-5 solutions Pharm. Res. 13 1142–1153 Occurrence Handle10.1023/A:1016043715791 Occurrence Handle8865303

    Article  PubMed  Google Scholar 

  39. R. G. Strickley B. D. Anderson (1997) ArticleTitleSolid-state stability of human insulin II. Effect of water on reactive intermediate partitioning in lyophiles from pH 2-5 solutions-stabilization against covalent dimer formation J. Pharm. Sci. 86 645–653 Occurrence Handle10.1021/js9700311 Occurrence Handle9188045

    Article  PubMed  Google Scholar 

  40. D. A. Case. AMBER 6, University of California, San Francisco, 1999.

  41. H. N. Cheng T. E. Smith D. M. Vitus (1981) ArticleTitleTacticity of poly(N-vinylpyrrolidinone) J. Polym. Sci., Polym. Lett. Ed. 19 29

    Google Scholar 

  42. J. R. Ebdon T. N. Huckerby E. Senogles (1983) ArticleTitleThe influence of polymerization conditions on the tacticity of poly(N-vinyl-2-pyrrolidone) Polymer 24 339–343 Occurrence Handle10.1016/0032-3861(83)90274-4

    Article  Google Scholar 

  43. J. M. Wang P. Cieplak P. A. Kollman (2000) ArticleTitleHow well does a restrained electrostatic potential (RESP) model perform in calculation conformational energies of organic and biological molecules? J. Comput. Chem. 12 1049–1074 Occurrence Handle10.1002/1096-987X(200009)21:12<1049::AID-JCC3>3.0.CO;2-F

    Article  Google Scholar 

  44. C. Simmerling B. Strockbine A. E. Roitberg (2002) ArticleTitleAll-atom structure prediction and folding simulations of a stable protein J. Am. Chem. Soc. 124 11258–11259 Occurrence Handle10.1021/ja0273851 Occurrence Handle12236726

    Article  PubMed  Google Scholar 

  45. W. D. Cornell P. Cieplak C. I. Bayly I. R. Gould K. M. Merz D. M. Ferguson D. C. Spellmeyer T. Fox J. W. Caldwell P. A. Kollman (1995) ArticleTitleA second generation force field for the simulation of proteins, nucleic acids, and organic molecules J. Am. Chem. Soc. 117 5179–5197 Occurrence Handle10.1021/ja00124a002

    Article  Google Scholar 

  46. Y. Duan C. Wu, S. Chowdhury M. C. Lee G. Xiong W. Zhang R. Yang P. Cieplak R. Luo T. Lee J. Caldwell J. Wang P. Kollman (2003) ArticleTitleA point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations J. Comp. Chem. 24 1999–2012 Occurrence Handle10.1002/jcc.10349

    Article  Google Scholar 

  47. A. D. Becke (1993) ArticleTitleDensity-functional thermochemistry. III. The role of exact exchange J. Chem. Phys. 98 5648–5652 Occurrence Handle10.1063/1.464913

    Article  Google Scholar 

  48. T. H. Dunning SuffixJr (1989) ArticleTitleGaussian basis sets for use in correlated molecular calculations. I. The atoms boron through neon and hydrogen J. Chem. Phys. 90 1007–1023 Occurrence Handle10.1063/1.456153

    Article  Google Scholar 

  49. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, V. G. Zakrzewski, J. A. Montgomery Jr., R. E. Stratmann, J. C. Burant, S. Dapprich, J. M. Millam, A. D. Daniels, K. N. Kudin, M. C. Strain, O. Farkas, J. Tomasi, V. Barone, M. Cossi, R. Cammi, B. Mennucci, C. Pomelli, C. Adamo, S. Clifford, J. Ochterski, G. A. Petersson, P. Y. Ayala, Q. Cui, K. Morokuma, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. Cioslowski, J. V. Ortiz, A. G. Baboul, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C.Y.Peng, A. Nanayakkara, C. Gonzalez, M. Challacombe, P.M.W. Gill, B. G. Johnson, W. Chen, M. W. Wong, J. L. Andres, M. Head-Gordon, E. S. Replogle, J. A. Pople. Gaussian 98 (Revision A.11), Gaussian, Inc., Pittsburgh PA, 2001.

  50. C. I. Bayly P. Cieplak W. D. Cornell P. A. Kollman (1993) ArticleTitleA well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: the RESP model J. Phys. Chem. 97 10269–10280 Occurrence Handle10.1021/j100142a004

    Article  Google Scholar 

  51. P. Cieplak W. D. Cornell C. Bayly P. A. Kollman (1995) ArticleTitleApplication of the multimolecule and multiconformational RESP methodology to biopolymers-charge derivation for DNA, RNA, and proteins J. Comput. Chem. 16 1357–1377 Occurrence Handle10.1002/jcc.540161106

    Article  Google Scholar 

  52. J. E. Eksterowicz J. L. Miller P. A. Kollman (1997) ArticleTitleCalculation of chloroform/water partition coefficients for the N-methylated nucleic acid bases J. Phys. Chem. B 101 10971–10975 Occurrence Handle10.1021/jp972440r

    Article  Google Scholar 

  53. T.-X. Xiang, B. D. Anderson. Conformational structure, dynamics and solvation free energies of small alanine peptides in water and carbon tetrachloride. J. Pharm. Sci. In press. (2005)

  54. L. Verlet (1967) ArticleTitleComputer “experiments” on classical fluids. I. Thermodynamical properties of Lennard-Jones molecules Phys. Rev. 159 98–103 Occurrence Handle10.1103/PhysRev.159.98

    Article  Google Scholar 

  55. H. J. C. Berendsen J. P. M. Postma W. F. Gunsteren Particlevan A. DiNola J. R. Haak (1984) ArticleTitleMolecular dynamics with coupling to an external bath J. Chem. Phys. 81 3684–3690 Occurrence Handle10.1063/1.448118

    Article  Google Scholar 

  56. P. Ewald (1921) ArticleTitleDie Berechnung optischer und elektrostatischer Gitterpotentiale Ann. Phys. 64 253–287

    Google Scholar 

  57. W. Humphrey A. Dalke K. Schulten (1996) ArticleTitleVMD-Visual Molecular Dynamics J. Mol. Graph. 14 33–38 Occurrence Handle10.1016/0263-7855(96)00018-5 Occurrence Handle8744570

    Article  PubMed  Google Scholar 

  58. T.-X. Xiang (1999) ArticleTitleTranslational diffusion in lipid bilayers: dynamic free-volume theory and molecular dynamics simulation J. Phys. Chem., B 103 385–394

    Google Scholar 

  59. S. H. Glarum (1960) ArticleTitleDielectric relaxation of isoamyl bromide J. Chem. Phys. 33 639–643 Occurrence Handle10.1063/1.1731229

    Article  Google Scholar 

  60. R. Kohlrausch (1854) ArticleTitleTheorie des electrischen Ruckstandes in der Leidner Flasche Pogg. Ann. Phys. Chem. 91 179–214

    Google Scholar 

  61. G. Williams D. C. Watts (1970) ArticleTitleNon-symmetrical dielectric relaxation behavior arising from a simple empirical decay function Trans. Faraday Soc. 66 80–85 Occurrence Handle10.1039/tf9706600080

    Article  Google Scholar 

  62. G. Williams D. C. Watts S. B. Dev A. M. North (1971) ArticleTitleFurther considerations of non symmetrical dielectric relaxation behaviour arising from a simple empirical decay function Trans. Faraday Soc. 67 1323–1335 Occurrence Handle10.1039/tf9716701323

    Article  Google Scholar 

  63. C. A. Angell (1995) ArticleTitleFormation of glasses from liquids and biopolymers Science 267 1924–1935

    Google Scholar 

  64. R. G. D. Valle H. C. Andersen (1992) ArticleTitleMolecular dynamics simulation of silica liquid and glass J. Chem. Phys. 97 2682–2689 Occurrence Handle10.1063/1.463056

    Article  Google Scholar 

  65. D. T. Turner A. Schwartz (1985) ArticleTitleThe glass transition temperature of poly(N-vinylpyrrolidone) by differential scanning calorimetry Polymer 26 757–762 Occurrence Handle10.1016/0032-3861(85)90114-4

    Article  Google Scholar 

  66. T. L. F. Lebedeva, M. Mikhail, A. K. Sergei, and A. Nicolai. A.V. Plate. The products of water H-bonding to poly(N-vinyl pyrrolidone) in solid state. In J. Greve, G. J. Puppels, and C.Otto (eds.), Spectroscopy of Biological Molecules: New Directions, European Conference on the Spectroscopy of Biological Molecules, 8th (J. Greve, G.J. Puppels, C. Otto, eds.), Enschede, Netherlands, 1999, pp. 581–582.

  67. F. Muller-Plathe (1998) ArticleTitleMicroscopic dynamics in water-swollen poly(vinyl alcohol) J. Chem. Phys. 108 8252–8263 Occurrence Handle10.1063/1.476180

    Article  Google Scholar 

  68. F. Franks (1981) Water solubility and sensitivity—hydration effects C. A. Finch (Eds) Chemistry and Technology of Water Soluble Polymers Plenum Press New York 157–178

    Google Scholar 

  69. M. J. Chang A. S. Myerson T. K. Kwei (1997) ArticleTitleThe effect of hydrogen bonding on vapor diffusion in water-soluble polymers J. Appl. Polym. Sci. 66 279–291 Occurrence Handle10.1002/(SICI)1097-4628(19971010)66:2<279::AID-APP9>3.0.CO;2-T

    Article  Google Scholar 

  70. O. Rodriguez F. Fornasiero A. Arce C. J. Radke J. M. Prausnitz (2003) ArticleTitleSolubilities and diffusivities of water vapor in poly(methylmethacrylate), poly(2-hydroxyethylmethacrylate), poly(N-vinyl-2-pyrrolidone) and poly(acrylonitrile) Polymer 44 6323–6333 Occurrence Handle10.1016/S0032-3861(03)00654-2

    Article  Google Scholar 

  71. Y. Wang G. Meresi D. Azar W.-Y. Wen A. A. Jones P. T. Inglefield (2001) ArticleTitleDiffusion of decafluropentane in amorphous glassy perflurodioxole copolymer by pulse field NMR spectroscopy Macromolecules 34 6680–6683 Occurrence Handle10.1021/ma010724a

    Article  Google Scholar 

  72. W. L. C. Vaz P. F. Almeida (1991) ArticleTitleMicroscopic versus macroscopic diffusion in one-component fluid phase lipid bilayer membranes Biophys. J. 60 1553–1554 Occurrence Handle1777573

    PubMed  Google Scholar 

  73. F. Mueller-Plathe S. C. Rogers W. F. Gunsteren Particlevan (1992) ArticleTitleComputational evidence for anomalous diffusion of small molecules in amorphous polymers Chem. Phys. Lett. 199 237–243 Occurrence Handle10.1016/0009-2614(92)80112-O

    Article  Google Scholar 

  74. K. Ichikawa T. Mori H. Kitano M. Fukuda A. Mochizuki M. Tanaka (2001) ArticleTitleFourier transform infrared study on the sorption of water to various kinds of polymer thin films J. Polym. Sci., B, Polym. Phys. 39 2175–2182

    Google Scholar 

  75. M. H. Cohen D. Turnbull (1959) ArticleTitleMolecular transport in liquids and glasses J. Chem. Phys. 31 1164–1169 Occurrence Handle10.1063/1.1730566

    Article  Google Scholar 

  76. T.-X. Xiang (1998) ArticleTitleA novel dynamic free-volume theory for molecular diffusion in fluids and interphases J. Chem. Phys. 109 7876–7884 Occurrence Handle10.1063/1.477434

    Article  Google Scholar 

Download references

Acknowledgments

This work was partially supported by a grant from the National Science Foundation, the Industry/University Cooperative Research Centers for Pharmaceutical Processing. The use of the computer resources at the Institute for High Performance Computing and the Center for Computational Sciences, University of Kentucky, is also acknowledged. The authors also appreciate the advice given by many members of the Amber and VMD discussion groups.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, 40536, USA

    Tian-Xiang Xiang & Bradley D. Anderson

Authors
  1. Tian-Xiang Xiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bradley D. Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bradley D. Anderson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xiang, TX., Anderson, B.D. Distribution and Effect of Water Content on Molecular Mobility in Poly(vinylpyrrolidone) Glasses: A Molecular Dynamics Simulation. Pharm Res 22, 1205–1214 (2005). https://doi.org/10.1007/s11095-005-5277-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-005-5277-5

Key Words

Search

Navigation