Electrospun Formulations Containing Crystalline Active Pharmaceutical Ingredients



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.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11





active pharmaceutical ingredient


differential scanning calorimetry




poly(vinyl pyrrolidone)


scanning electron microscopy


X-ray diffraction

A :

surface area for diffusion

C :

concentration in solution

C sat :


D :

diffusion coefficient

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

dissolution rate

g :

gravitational acceleration

h :

diffusional path length

ρ f :

density of the fluid

ρ p :

density of the particle

R :

radius of the particle

μ :

viscosity of the fluid

v s :

settling velocity


  1. 1.

    Plumb K. Continuous processing in the pharmaceutical industry: Changing the mind set. Chem Eng Res Des. 2005;83(6):730–8.

    Article  CAS  Google Scholar 

  2. 2.

    Breitenbach J. Melt extrusion: from process to drug delivery technology. Eur J Pharm Biopharm. 2002;54(2):107–17.

    PubMed  Article  CAS  Google 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.

  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.

  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.

    PubMed  Article  CAS  Google 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.

    Article  CAS  Google 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.

    Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Ramakrishna S. An Introduction to Electrospinning and Nanofibers. Singapore: World Scientific Publishing Company; 2005.

    Google 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.

    Article  Google Scholar 

  12. 12.

    Yarin AL, Zussman E. Upward needleless electrospinning of multiple nanofibers. Polymer. 2004;45(9):2977–80.

    Article  CAS  Google 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.

    Article  Google Scholar 

  14. 14.

    Kostakova E, Meszaros L, Gregr J. Composite nanofibers produced by modified needleless electrospinning. Mater Lett. 2009;63(28):2419–22.

    Article  CAS  Google 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.

  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.

    Article  CAS  Google 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.

    Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    CAS  Google Scholar 

  20. 20.

    Forward KM, Rutledge GC. Free surface electrospinning from a wire electrode. Chem Eng J. 2012;183:492–503.

    Article  CAS  Google 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.

    Article  CAS  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Wang M, Singh H, Hatton TA, Rutledge GC. Field-responsive superparamagnetic composite nanofibers by electrospinning. Polymer. 2004;45(16):5505–14.

    Article  CAS  Google Scholar 

  28. 28.

    Tiwari MK, Yarin AL, Megaridis CM. Electrospun fibrous nanocomposites as permeable, flexible strain sensors. J Appl Phys. 2008;103(4):044305.

    Article  Google 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.

    PubMed  Article  CAS  Google 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.

    Article  CAS  Google 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.

    Article  CAS  Google 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.

    PubMed  Article  CAS  Google 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.

    PubMed  Article  CAS  Google Scholar 

  34. 34.

    U.S. Pharmacopeia Reference Tables. USP29-NF24. www.pharmacopeia.cn. 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.

    Article  CAS  Google 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.

    PubMed  CAS  Google 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.

    Article  CAS  Google Scholar 

  38. 38.

    Cambridge Structural Database, reference code BOGFUZ

  39. 39.

    Cambridge Structural Database, reference code FOGVIG06

  40. 40.

    Cambridge Structural Database, reference code FOGVIG07

  41. 41.

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

    PubMed  Article  CAS  Google 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.

    PubMed  Article  Google Scholar 

Download references


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.

Author information



Corresponding author

Correspondence to Bernhardt L. Trout.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Brettmann, B.K., Cheng, K., Myerson, A.S. et al. Electrospun Formulations Containing Crystalline Active Pharmaceutical Ingredients. Pharm Res 30, 238–246 (2013). https://doi.org/10.1007/s11095-012-0868-4

Download citation


  • crystals
  • electrospinning
  • formulation
  • solid dispersion