Pharmaceutical Research

, Volume 30, Issue 1, pp 238–246 | Cite as

Electrospun Formulations Containing Crystalline Active Pharmaceutical Ingredients

  • Blair Kathryn Brettmann
  • Kamyu Cheng
  • Allan S. Myerson
  • Bernhardt L. Trout
Research Paper



To investigate the use of electrospinning for forming solid dispersions containing crystalline active pharmaceutical ingredients (API) and understand the relevant properties of the resulting materials.


Free surface electrospinning was used to prepare nanofiber mats of poly(vinyl pyrrolidone) (PVP) and crystalline albendazole (ABZ) or famotidine (FAM) from a suspension of the drug crystals in a polymer solution. SEM and DSC were used to characterize the dispersion, XRD was used to determine the crystalline polymorph, and dissolution studies were performed to determine the influence of the preparation method on the dissolution rate.


The electrospun fibers contained 31 wt% ABZ and 26 wt% FAM for the 1:2 ABZ:PVP and 1:2 FAM:PVP formulations, respectively, and both APIs retained their crystalline polymorphs throughout processing. The crystals had an average size of about 10 μm and were well-dispersed throughout the fibers, resulting in a higher dissolution rate for electrospun tablets than for powder tablets.


Previously used to produce amorphous formulations, electrospinning has now been demonstrated to be a viable option for producing fibers containing crystalline API. Due to the dispersion of the crystals in the polymer, tablets made from the fiber mats may also exhibit improved dissolution properties over traditional powder compression.


crystals electrospinning formulation solid dispersion 





active pharmaceutical ingredient


differential scanning calorimetry




poly(vinyl pyrrolidone)


scanning electron microscopy


X-ray diffraction


surface area for diffusion


concentration in solution




diffusion coefficient

\( \frac{{dm}}{{dt}} \)

dissolution rate


gravitational acceleration


diffusional path length


density of the fluid


density of the particle


radius of the particle


viscosity of the fluid


settling velocity



We would like to acknowledge Novartis AG for funding and support of this work. We would also like to thank Keith M. Forward for aid with free-surface electrospinning and Keith Chadwick for his input on XRD interpretation.


  1. 1.
    Plumb K. Continuous processing in the pharmaceutical industry: Changing the mind set. Chem Eng Res Des. 2005;83(6):730–8.CrossRefGoogle Scholar
  2. 2.
    Breitenbach J. Melt extrusion: from process to drug delivery technology. Eur J Pharm Biopharm. 2002;54(2):107–17.PubMedCrossRefGoogle Scholar
  3. 3.
    Bell ER, Massachusetts Institute of Technology. Melt extrusion and continuous manufacturing of pharmaceutical materials [PhD Thesis]. Cambridge, MA: Massachusetts Institute of Technology; 2011.Google Scholar
  4. 4.
    Kim W, Massachusetts Institute of Technology. Layer bonding of solvent-cast thin films for pharmaceutical solid dosage forms [Master’s Thesis]. Cambridge, MA: Massachusetts Institute of Technology; 2010.Google Scholar
  5. 5.
    Brettmann BK, Bell E, Myerson AS. and Trout B L, Solid-state NMR characterization of high-loading solid solutions of API and excipients formed by electrospinning. J Pharm Sci. 2012;101(4):1538–45.PubMedCrossRefGoogle Scholar
  6. 6.
    Buschle-Diller G, Cooper J, Xie Z, Wu Y, Waldrup J. Release of antibiotics from electrospun bicomponent fibers. Cellulose. 2007;14:553–62.CrossRefGoogle Scholar
  7. 7.
    Yu D, Zhang X, Shen X. Brandford–White C, Zhu L. Ultrafine ibuprofen–loaded polyvinylpyrrolidone fiber mats using electrospinning. Polym Int. 2009;58:1010–3.CrossRefGoogle Scholar
  8. 8.
    Verreck G, Chun I, Peeters J, Rosenblatt J, Brewster ME. Preparation and characterization of nanofibers containing amorphous drug dispersions generated by electrostatic spinning. Pharm Res. 2003;20:810–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Verreck G, Chun I, Rossenblatt J, Peeters J, Van Dijck A, Mensch J, Noppe M, Brewster ME. Incorporation of drugs in an amorphous state into electrospun nanofibers composed of a water-insoluble, nonbiodegradable polymer. J Control Release. 2003;92:349–60.PubMedCrossRefGoogle Scholar
  10. 10.
    Ramakrishna S. An Introduction to Electrospinning and Nanofibers. Singapore: World Scientific Publishing Company; 2005.CrossRefGoogle Scholar
  11. 11.
    Lukas D, Sarkar A, Pokorny P. Self-organization of jets in electrospinning from free liquid surface: a generalized approach. J Appl Phys. 2008;103(8):084309.CrossRefGoogle Scholar
  12. 12.
    Yarin AL, Zussman E. Upward needleless electrospinning of multiple nanofibers. Polymer. 2004;45(9):2977–80.CrossRefGoogle Scholar
  13. 13.
    Miloh T, Spivak B, Yarin AL. Needleless electrospinning: electrically driven instability and multiple jetting from the free liquid surface of a spherical liquid layer. J Appl Phys. 2009;106(11):114910.CrossRefGoogle Scholar
  14. 14.
    Kostakova E, Meszaros L, Gregr J. Composite nanofibers produced by modified needleless electrospinning. Mater Lett. 2009;63(28):2419–22.CrossRefGoogle Scholar
  15. 15.
    Jirsak O, Sysel P, Sanetrnik F, Hruza J, Chaloupek J. Polyamic acid nanofibers produced by needleless electrospinning. J Nanomater. 2010 Jan; ID842831.Google Scholar
  16. 16.
    Niu H, Lin T, Wang X. Needleless electrospinning. I. a comparison of cylinder and disk nozzles. J Appl Polym Sci. 2009;114(6):3524–30.CrossRefGoogle Scholar
  17. 17.
    Wang X, Niu H, Lin T. Needleless electrospinning of nanofibers with a conical wire coil. Polym Engr Sci. 2009;49(8):1582–6.CrossRefGoogle Scholar
  18. 18.
    Lu B, Wang Y, Liu Y, Duan H, Zhou J, Zhang Z, Wang Y, Li X, Wang W, Lan E. Superhigh-throughput needleless electrospinning using a rotary cone as spinneret. Small. 2010;6(15):1612–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Varabhas JS, Tripatanasuwan S, Chase GG, Reneker DH. Electrospun jets launched from polymeric bubbles. J Eng Fibers Fabr. 2009;4:46–50.Google Scholar
  20. 20.
    Forward KM, Rutledge GC. Free surface electrospinning from a wire electrode. Chem Eng J. 2012;183:492–503.CrossRefGoogle Scholar
  21. 21.
    Tungprapa S, Jangchud I, Supaphol P. Release characteristics of four model drugs from drug-loaded electrospun cellulose acetate fiber mats. Polymer. 2007;48(17):5030–41.CrossRefGoogle Scholar
  22. 22.
    Yu DG, Shen XX, Branford-White C, White K, Zhu LM, Bligh SWA. Oral fast-dissolving drug delivery membranes prepared from electrospun polyvinylpyrrolidone ultrafine fibers. Nanotechnology. 2009;20(5):055104.PubMedCrossRefGoogle Scholar
  23. 23.
    Hancock BC, Zografi G. Characteristics and significance of the amorphous state in pharmaceutical systems. J Pharm Sci. 1997;86(1):1–12.PubMedCrossRefGoogle Scholar
  24. 24.
    Chew SY, Hufnagel TC, Lim CT, Leong KW. Mechanical properties of single electrospun drug-encapsulated nanofibres. Nanotechnology. 2006;17(15):3880–91.PubMedCrossRefGoogle Scholar
  25. 25.
    Natu MV, de Sousa HC, Gil MH. Effects of drug solubility, state and loading on controlled release in bicomponent electrospun fibers. Int J Pharm. 2010;397(1–2):50–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Ignatious F, Sun L, Lee C-P, Baldoni J. Electrospun nanofibers in oral drug delivery. Pharm Res. 2010;27(4):576–88.PubMedCrossRefGoogle Scholar
  27. 27.
    Wang M, Singh H, Hatton TA, Rutledge GC. Field-responsive superparamagnetic composite nanofibers by electrospinning. Polymer. 2004;45(16):5505–14.CrossRefGoogle Scholar
  28. 28.
    Tiwari MK, Yarin AL, Megaridis CM. Electrospun fibrous nanocomposites as permeable, flexible strain sensors. J Appl Phys. 2008;103(4):044305.CrossRefGoogle Scholar
  29. 29.
    Salalha W, Kuhn J, Dror Y, Zussman E. Encapsulation of bacteria and viruses in electrospun nanofibers. Nanotechnology. 2006;17(18):4675–81.PubMedCrossRefGoogle Scholar
  30. 30.
    Wang M, Hsieh AJ, Rutledge GC. Electrospinning of poly(MMA-co-MAA) copolymers and their layered silicate nanocomposites for improved thermal properties. Polymer. 2005;46(10):3407–18.CrossRefGoogle Scholar
  31. 31.
    Wang M, Yu JH, Hsieh AJ, Rutledge GC. Effect of tethering chemistry of cationic surfactants on clay exfoliation, electrospinning and diameter of PMMA/clay nanocomposite fibers. Polymer. 2010;51(26):6295–302.CrossRefGoogle Scholar
  32. 32.
    Brettmann B, Tsang S, Forward K, Rutledge G, Myerson AS, Trout BL. Free Surface Electrospinning of Microparticles. Langmuir. 2012;28(25):9714–21.PubMedCrossRefGoogle Scholar
  33. 33.
    Lim J-M, Moon JH, Yi G-R, Heo C-J, Yang S-M. Fabrication of one-dimensional colloidal assemblies from electrospun nanofibers. Langmuir. 2006;22(8):3445–9.PubMedCrossRefGoogle Scholar
  34. 34.
    U.S. Pharmacopeia Reference Tables. USP29-NF24. Accessed Aug 5, 2012.
  35. 35.
    Dror Y, Salalha W, Khalfin RL, Cohen Y, Yarin AL, Zussman E. Carbon nanotubes embedded in oriented polymer nanofibers by electrospinning. Langmuir. 2003;19(17):7012–20.CrossRefGoogle Scholar
  36. 36.
    Pranzo MB, Cruickshank D, Coruzzi M, Caira MR, Bettini R. Enantiotropically related albendazole polymorphs. J Pharm Sci. 2010;99(9):3731–41.PubMedGoogle Scholar
  37. 37.
    Lu J, Wang X-J, Yang X, Ching C-B. Polymorphism and Crystallization of Famotidine. Cryst Growth Des. 2007;7(9):1590–8.CrossRefGoogle Scholar
  38. 38.
    Cambridge Structural Database, reference code BOGFUZGoogle Scholar
  39. 39.
    Cambridge Structural Database, reference code FOGVIG06Google Scholar
  40. 40.
    Cambridge Structural Database, reference code FOGVIG07Google Scholar
  41. 41.
    Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm. 2000;50:47–60.PubMedCrossRefGoogle Scholar
  42. 42.
    Marsac PJ, Li T, Taylor LS. Estimation of drug–polymer miscibility and solubility in amorphous solid dispersions using experimentally determined interaction parameters. Pharm Res. 2008;26(1):139–51.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Blair Kathryn Brettmann
    • 1
  • Kamyu Cheng
    • 1
  • Allan S. Myerson
    • 1
  • Bernhardt L. Trout
    • 1
  1. 1.Department of Chemical EngineeringMassachusetts Institute of TechnologyCambridgeUSA

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