Micro-Computed Tomography (Micro-CT) Analysis as a New Approach for Characterization of Drug Delivery Systems

  • Müge Kılıçarslan
  • Miray Ilhan
  • Kaan Orhan


In this chapter, examples from the limited number of studies conducted on the use of micro-CT analysis method, which has been previously used in various areas, for the in vitro and/or in vivo characterization of drug delivery systems are presented, and the possibility of using micro-CT on characterization of drug delivery systems (granule, tablet, dome matrix, micro- and nanoparticle, scaffold, film, implant, in situ implant, etc.) is evaluated. In addition, some of the in vitro micro-CT analysis data on different types of drug delivery systems (complex film and nanoparticle) prepared by our study group is presented, and the future advantages and disadvantages of micro-CT analyses used in the evaluation of drug formulations are discussed within the scope of these experiences. Based on the results of our study, it is found that the ability to perform several quantitative analyses such as size and volume analysis rather than just three-dimensional imaging may provide ease of use by working with a simple method instead of multiple methods during the development phase of the formulation and may guide the study on a sounder basis despite the disadvantages of the method such as the resolution of the device, duration of the analysis period, and high cost.


Micro-CT Drug delivery Microsphere Nanoparticle Scaffold Tablet Matrix system Implant 



This research has been supported by Ankara University Scientific Research Projects Coordination Unit (grant number, 17A0234001; continued; grant number, 17H0237006, 2017).

Supplementary material

Movie Picture 13.1

3D Micro-CT movie of PEC film (F1) (AVI 3515989 kb)


  1. 1.
    Gauthier O, Muller R, von Stechow D, Lamy B, Weiss P, Bouler JM, et al. In vivo bone regeneration with injectable calcium phosphate biomaterial: a three-dimensional micro-computed tomographic, biomechanical and SEM study. Biomaterials. 2005;26:5444–53.CrossRefGoogle Scholar
  2. 2.
    Zhou H, Hernandez C, Goss M, Gawlik A, Exner AA. Biomedical imaging in implantable drug delivery systems. Curr Drug Targets. 2015;16:672–82.CrossRefGoogle Scholar
  3. 3.
    Ho ST, Hutmacher DW. A comparison of micro CT with other techniques used in the characterization of scaffolds. Biomaterials. 2006;27:1362–76.CrossRefGoogle Scholar
  4. 4.
    Williams JM, Adewunmi A, Schek RM, Flanagan CL, Krebsbach PH, Feinberg SE, et al. Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering. Biomaterials. 2005;26:4817–27.CrossRefGoogle Scholar
  5. 5.
    Jones JR, Poologasundarampillai G, Atwood RC, Bernard D, Lee PD. Non-destructive quantitative 3D analysis for the optimisation of tissue scaffolds. Biomaterials. 2007;28:1404–13.CrossRefGoogle Scholar
  6. 6.
    De Santis R, Gloria A, Russo T, D’Amora U, Zeppetelli S, Tampieri A, et al. A route toward the development of 3D magnetic scaffolds with tailored mechanical and morphological properties for hard tissue regeneration: preliminary study. Virtual Phys Prototyping. 2011;6:189–95.CrossRefGoogle Scholar
  7. 7.
    Lin AS, Barrows TH, Cartmell SH, Guldberg RE. Microarchitectural and mechanical characterization of oriented porous polymer scaffolds. Biomaterials. 2003;24:481–9.CrossRefGoogle Scholar
  8. 8.
    Wang F, Shor L, Darling A, Khalil S, Sun W, Güçeri S, et al. Precision extruding deposition and characterization of cellular poly-ε-caprolactone tissue scaffolds. Rapid Prototyp J. 2004;10:42–9.CrossRefGoogle Scholar
  9. 9.
    Wang Y, Chang HI, Wertheim DF, Jones AS, Jackson C, Coombes AG. Characterisation of the macroporosity of polycaprolactone-based biocomposites and release kinetics for drug delivery. Biomaterials. 2007;28:4619–27.CrossRefGoogle Scholar
  10. 10.
    Wang Y, Wertheim DF, Jones AS, Chang HI, Coombes AG. Micro-CT analysis of matrix-type drug delivery devices and correlation with protein release behaviour. J Pharm Sci. 2010;99:2854–62.CrossRefGoogle Scholar
  11. 11.
    Wang Y, Wertheim DF, Jones AS, Coombes AG. Micro-CT in drug delivery. Eur J Pharm Biopharm. 2010;74:41–9.CrossRefGoogle Scholar
  12. 12.
    Krebs MD, Sutter KA, Lin AS, Guldberg RE, Alsberg E. Injectable poly(lactic-co-glycolic) acid scaffolds with in situ pore formation for tissue engineering. Acta Biomater. 2009;5:2847–59.CrossRefGoogle Scholar
  13. 13.
    Balmayor ER, Tuzlakoglu K, Azevedo HS, Reis RL. Preparation and characterization of starch-poly-epsilon-caprolactone microparticles incorporating bioactive agents for drug delivery and tissue engineering applications. Acta Biomater. 2009;5:1035–45.CrossRefGoogle Scholar
  14. 14.
    Patel ZS, Yamamoto M, Ueda H, Tabata Y, Mikos AG. Biodegradable gelatin microparticles as delivery systems for the controlled release of bone morphogenetic protein-2. Acta Biomater. 2008;4:1126–38.CrossRefGoogle Scholar
  15. 15.
    Son JS, Appleford M, Ong JL, Wenke JC, Kim JM, Choi SH, et al. Porous hydroxyapatite scaffold with three-dimensional localized drug delivery system using biodegradable microspheres. J Control Release. 2011;153:133–40.CrossRefGoogle Scholar
  16. 16.
    Lin L, Wang T, Zhou Q, Qian N. The effects of different amounts of drug microspheres on the vivo and vitro performance of the PLGA/beta-TCP scaffold. Des Monomers Polym. 2017;20:351–62.CrossRefGoogle Scholar
  17. 17.
    Farber L, Tardos G, Michaels JN. Use of X-ray tomography to study the porosity and morphology of granules. Powder Technol. 2003;132:57–63.CrossRefGoogle Scholar
  18. 18.
    Doerr F, Brammer E, Wood S, Halbert G, Florence A. Morphological Characterisation of Solid Pharmaceutical Products using X-ray tomography. Bruker SkyScan Micro-CT User Meeting 2017; 2017.Google Scholar
  19. 19.
    Sinka IC, Burch SF, Tweed JH, Cunningham JC. Measurement of density variations in tablets using X-ray computed tomography. Int J Pharm. 2004;271:215–24.CrossRefGoogle Scholar
  20. 20.
    Busignies V, Leclerc B, Porion P, Evesque P, Couarraze G, Tchoreloff P. Quantitative measurements of localized density variations in cylindrical tablets using X-ray microtomography. Eur J Pharm Biopharm. 2006;64:38–50.CrossRefGoogle Scholar
  21. 21.
    Losi E, Peppas NA, Ketcham RA, Colombo G, Bettini R, Sonvico F, et al. Investigation of the swelling behavior of Dome Matrix drug delivery modules by high-resolution X-ray computed tomography. J Drug Deliv Sci Technol. 2013;23:165–70.CrossRefGoogle Scholar
  22. 22.
    Haesslein A, Ueda H, Hacker MC, Jo S, Ammon DM, Borazjani RN, et al. Long-term release of fluocinolone acetonide using biodegradable fumarate-based polymers. J Control Release. 2006;114:251–60.CrossRefGoogle Scholar
  23. 23.
    Kilicarslan M, Ilhan M, Inal O, Orhan K. Preparation and evaluation of clindamycin phosphate loaded chitosan/alginate polyelectrolyte complex film as mucoadhesive drug delivery system for periodontal therapy. Eur J Pharm Sci. 2018;123:441–51.CrossRefGoogle Scholar
  24. 24.
    Feldkamp LA, Goldstein SA, Parfitt AM, Jesion G, Kleerekoper M. The direct examination of three-dimensional bone architecture in vitro by computed tomography. J Bone Miner Res. 1989;4:3–11.CrossRefGoogle Scholar
  25. 25.
    Abdelkader DH, El-Gizawy SA, Faheem AM, McCarron PA, Osman MA. Effect of process variables on formulation, in-vitro characterisation and subcutaneous delivery of insulin PLGA nanoparticles: an optimisation study. J Drug Deliv Sci Technol. 2018;43:160–71.CrossRefGoogle Scholar
  26. 26.
    Reix N, Parat A, Seyfritz E, Van der Werf R, Epure V, Ebel N, et al. In vitro uptake evaluation in Caco-2 cells and in vivo results in diabetic rats of insulin-loaded PLGA nanoparticles. Int J Pharm. 2012;437:213–20.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Müge Kılıçarslan
    • 1
  • Miray Ilhan
    • 1
  • Kaan Orhan
    • 2
    • 3
    • 4
  1. 1.Faculty of Pharmacy, Department of Pharmaceutical TechnologyAnkara UniversityAnkaraTurkey
  2. 2.Faculty of Dentistry, Department of Dentomaxillofacial RadiologyAnkara UniversityAnkaraTurkey
  3. 3.Faculty of Medicine, OMFS IMPATH Research Group, Department of Imaging and PathologyUniversity of LeuvenLeuvenBelgium
  4. 4.Oral and Maxillofacial Surgery, University Hospitals LeuvenUniversity of LeuvenLeuvenBelgium

Personalised recommendations