Skip to main content
SpringerLink
Log in

Continuous Generation of Ethyl Cellulose Drug Delivery Nanocarriers from Microbubbles

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

Abstract

Purpose

To investigate a new microfluidic method for the continuous preparation of hollow-shell nanoparticles of a hydrophobic polymer and the simultaneous encapsulation within these of a hydrophilic active pharmaceutical ingredient.

Method

A specially designed and constructed microfluidic device which facilitates at a junction the impingement of two liquids flowing in capillaries kept 60° apart, one containing the polymer ethyl cellulose (EC) and the other active pharmaceutical ingredient amoxicillin, and a gas flowing in a capillary bisecting the two liquid flows, was used to continuously generate EC coated microbubbles at an outlet directly below the gas flow. The bubbles produce EC nanoparticles whilst encapsulating amoxicillin, and these were characterised by microscopy, zeta potential measurements, FTIR and UV spectroscopy and in vitro drug release and kinetic studies.

Results

The device produced ~5 × 106 microbubbles per minute from the surface of which EC nanocarriers were released spontaneously according to an evaporation-controlled mechanism. The gas pressure was very effective in controlling the size and size distribution of the nanocarriers.

Conclusions

Nanocarriers with diameter between 10 and 800 nm were continuously produced by controlling the gas pressure between 110 and 510 kPa. Depending on their size, particles were capable of encapsulating 65–88% of amoxicillin which was released over ~12 h.

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
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

References

  1. Dendukuri D, Doyle PS. The synthesis and assembly of polymeric microparticles using microfluidics. Adv Mater. 2009;21:1–16.

    Article  Google Scholar 

  2. Zhang C, Xu J, Ma W, Zheng W. PCR microfluidic devices for DNA amplification. Biotech Adv. 2006;24:243–84.

    Article  CAS  Google Scholar 

  3. Zheng B, Tice JD, Roach LS, Ismagilov RF. A droplet-based, composite PDMS/glass capillary microfluidic system for evaluating protein crystallization conditions by microbatch and vapor-diffusion methods with on-chip x-ray diffraction. Angew Chem Int Ed. 2004;43:2508–11.

    Article  CAS  Google Scholar 

  4. Fang A, Cathala B. Smart swelling biopolymer microparticles by a microfluidic approach: synthesis, in situ encapsulation and controlled release. Coll Surf B: Biointerfaces. 2011;82:81–6.

    Article  CAS  Google Scholar 

  5. Hung L-H, Teh S-Y, Jester J, Lee AP. PLGA micro/nanosphere synthesis by droplet microfluidic solvent evaporation and extraction approaches. Lab Chip. 2010;10:1820–5.

    Article  PubMed  CAS  Google Scholar 

  6. Barratt G. Colloidal drug carriers: achievements and perspectives. Cell Mol Life Sci. 2003;60:21–37.

    Article  PubMed  CAS  Google Scholar 

  7. Reverchon E. Supercritical antisolvent precipitation of micro- and nano- particles. J Supercrit Fluids. 1999;15:1–21.

    Article  CAS  Google Scholar 

  8. Lui L, Yang J-P, Ju X-J, Xie R, Yang L, Liang B, et al. Microfluidic preparation of monodisperse ethyl cellulose hollow microcapsules with non-toxic solvent. J Coll Interf Sci. 2009;336:100–6.

    Article  Google Scholar 

  9. Song M, Li N, Sun S, Tiedt LR, Liebenberg W, de Villiers MM. Effect of viscosity and concentration of wall former, emulsifier and pore-inducer on the properties of amoxicillin microcapsules prepared by emulsion solvent evaporation. Il Farmaco. 2005;60:261–7.

    Article  CAS  Google Scholar 

  10. Siepmann J, Peppas NA. Higuchi equation: derivation, applications, use and misuse. Int J Pharm. 2011;418:6–12.

    Article  PubMed  CAS  Google Scholar 

  11. Higuchi T. Mechanism of sustained- action medication Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963;52:1145–9.

    Article  PubMed  CAS  Google Scholar 

  12. Parikh NH, Porter SC, Rohera BD. Aqueous ethylcellulose dispersion of ethylcellulose. I. Evaluation of coating process variables. Pharmaceut Res. 1993;10:525–34.

    Article  CAS  Google Scholar 

  13. Lin W-J, Wu T-L. Modification of the initial release of a highly water-soluble drug from ethyl cellulose microspheres. J Microencapsul. 1999;16:639–46.

    Article  PubMed  CAS  Google Scholar 

  14. Crowley MM, Schroeder B, Fredersdorf A, Obara S, Talarico M, Kucera S, et al. Physcochemical properties and mechanism of drug release from ethyl cellulose matrix tablets prepared by direct compression and hot-melt extrusion. Int J Pharm. 2004;269:509–22.

    Article  PubMed  CAS  Google Scholar 

  15. Bruno L, Kasapis S, Chaudhary V, Chow KT, Heng PWS, Leong LP. Temperature and time effects on the structural properties of a non-aqueous ethyl cellulose drug delivery system. Carb Poly. 2011;86:644–51.

    Article  CAS  Google Scholar 

  16. Appel LE, Zentner GM. Use of modified ethycellulose lattices for microporous coating of osmotic tablets. Pharmaceut Res. 1991;8:600–4.

    Article  CAS  Google Scholar 

  17. Kang MK, Kim J-C. pH-dependent release from ethylcellulose microparticles containing alginate and calcium carbonate. Coll Poly Sci. 2010;288:265–270.

    Article  CAS  Google Scholar 

  18. Murtaza G. Ethylcellulose microparticles: a review. Acta Poloniae Pharm Drug Res. 2012;69:11–22.

    CAS  Google Scholar 

  19. Montes A, Gordillo MD, Pereyra EJ, de la Ossa M. Co-precipitation of amoxicillin and ethyl cellulose microparticles by supercritical antisolvent process. J Supercrit Fluids. 2011;60:75–80.

    Article  CAS  Google Scholar 

  20. Choy YB, Choi H, Kim K. Uniform ethyl cellulose microspheres of controlled sizes and polymer viscosities and their drug-release profiles. J Appl Polym Sci. 2009;112:850–7.

    Article  CAS  Google Scholar 

  21. Khan SA, Ahmad M, Murtaza G, Aamir MN, Madni A, Kousar R, Minhas U. Development of a single combined microencapsulated formulation of allopurinol and nimesulide and investigation of their release behaviours. Ars Pharm. 2010;51:105–16.

    Google Scholar 

  22. Hu L, Liu W, Li L, Zhao J, Yang X. Preparation and in vitro, in vivo evaluation of clarithromycin microcapsules. J Basic Clin Pharm. 2011;2:1–9.

    CAS  Google Scholar 

  23. Pancholi K, Stride E, Edirisinghe M. Dynamics of bubble formation in highly viscous liquids. Langmuir. 2008;24:4388–93.

    Article  PubMed  CAS  Google Scholar 

  24. Gunduz O, Ahmad Z, Stride E, Tamerler C, Edirisinghe M. Bioinspired bubble design for particle generation. J Roy Soc Interface. 2012;9:389–95.

    Article  CAS  Google Scholar 

  25. Gunduz O, Ahmad Z, Stride E, Edirisinghe M. A device for the fabrication of multifunctional particles from microbubble suspensions. J Mat Sci Eng C. 2012;32:1005–10.

    Article  CAS  Google Scholar 

  26. Stride E, Pancholi K, Edirisinghe M, Samarasinghe S. Increasing the non-linear character of microbubble oscillations at low acoustic pressures. J Roy Soc Interface. 2008;5:807–11.

    Article  CAS  Google Scholar 

  27. Huang L-Y, Yu D-G, Branford-White C, Zhu L-M. Sustained release of ethyl cellulose micro-particle drug delivery systems prepared using electrospraying. J Mater Sci. 2012;47:1372–7.

    Google Scholar 

  28. Kalogiannis CG, Michailof CM, Panayiotou CG. Microencapsulation of amoxicillin in poly(L-lactic acid) by supercritical antisolvent precipitation. Ind Eng Chem Res. 2006;45:8738–43.

    Article  CAS  Google Scholar 

  29. Xu Q, Hashimoto M, Dang TT, Hoare T, Kohane DS, Whitesides GM, et al. Preparation of monodisperse biodegradable polymer microparticles using a microfluidic flow-focusing device for controlled drug delivery. Small. 2009;5:1575–81.

    Article  PubMed  CAS  Google Scholar 

  30. Moine P, Mazoit JX. Streptococcus pneumoniae pneumonia in mice: Optimal amoxicillin dosing predicted from a pharmacokinetic-pharmacodynamic model. J Pharmacol Exp Ther. 1999;291:1086–92.

    PubMed  CAS  Google Scholar 

  31. Wagh SC, Kumar JS, Banerjee S. Development and evaluation of a novel extended release venlafaxine hydrochloride matrix tablets. J Pharm Res. 2012;5:2184–90.

    CAS  Google Scholar 

  32. Pahwa R, Chhabra L, Lamba AK, Jindal S, Rathour A. Formulation and in-vitro evaluation of effervescent floating tablets of an antiulcer agent. J Chem Pharm Res. 2012;4:1066–73.

    CAS  Google Scholar 

  33. Bohr A, Kristensen J, Dyas M, Edirisinghe M, Stride E. Release profile and characteristics of electrosprayed particles for oral delivery of a practically insoluble drug. J R Soc Interface. 2012. doi:10.1098/rsif.2012.0166.

Download references

Acknowledgments and Disclosures

The authors wish to thank the Islamic Development Bank for supporting the doctoral research programme of Oguzhan Gunduz. They would also like to thank Kevin Reeves for the help with the scanning electron microscopes in the Archaeology Department at UCL and Dr Suguo Huo of the London Centre for Nanotechnology for the use of FIB.

Author information

Authors and Affiliations

  1. Department of Mechanical Engineering, University College London, Torrington Place, London, WC1E 7JE, UK

    Oguzhan Gunduz, Eleanor Stride & Mohan Edirisinghe

  2. Materials Department, Technical Education Faculty, Marmara University, Goztepe, Istanbul, 34722, Turkey

    Oguzhan Gunduz

  3. School of Pharmacy and Biomedical Sciences, University of Portsmouth, St. Michaels Building, White Swan Road, Portsmouth, PO1 2DT, UK

    Zeeshan Ahmad

  4. Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Old Road Campus, Oxford, OX3 7DQ, UK

    Eleanor Stride

Authors
  1. Oguzhan Gunduz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zeeshan Ahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eleanor Stride
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mohan Edirisinghe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohan Edirisinghe.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Video: Supplementary video showing the device and process.

(WMV 551 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gunduz, O., Ahmad, Z., Stride, E. et al. Continuous Generation of Ethyl Cellulose Drug Delivery Nanocarriers from Microbubbles. Pharm Res 30, 225–237 (2013). https://doi.org/10.1007/s11095-012-0865-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-012-0865-7

KEY WORDS

Search

Navigation