Colorimetry as Quality Control Tool for Individual Inkjet-Printed Pediatric Formulations


Printing technologies were recently introduced to the pharmaceutical field for manufacturing of drug delivery systems. Printing allows on demand manufacturing of flexible pharmaceutical doses in a personalized manner, which is critical for a successful and safe treatment of patient populations with specific needs, such as children and the elderly, and patients facing multimorbidity. Printing of pharmaceuticals as technique generates new demands on the quality control procedures. For example, rapid quality control is needed as the printing can be done on demand and at the point of care. This study evaluated the potential use of a handheld colorimetry device for quality control of printed doses of vitamin Bs on edible rice and sugar substrates. The structural features of the substrates with and without ink were also compared. A multicomponent ink formulation with vitamin B1, B2, B3, and B6 was developed. Doses (4 cm2) were prepared by applying 1–10 layers of yellow ink onto the white substrates using thermal inkjet technology. The colorimetric method was seen to be viable in detecting doses up to the 5th and 6th printed layers until color saturation of the yellow color parameter (b*) was observed on the substrates. Liquid chromatography mass spectrometry was used as a reference method for the colorimetry measurements plotted against the number of printed layers. It was concluded that colorimetry could be used as a quality control tool for detection of different doses. However, optimization of the color addition needs to be done to avoid color saturation within the planned dose interval.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5


  1. 1.

    World Health Organization. Guidelines on submission of documentation for a multisource (generic) finished pharmaceutical product for the WHO Prequalification of Medicines Program: quality part. WHO Expert Committee on Specifications for Pharmaceutical Preparations. 46th report. Geneva. 2012; Annex 5:200–204. Accessed 12 Aug 2016.

  2. 2.

    Ernest TB, Craig J, Nunn A, Salunke S, Tuleu C, Breitkreutz J, et al. Preparation of medicines for children—a hierarchy of classification. Int J Pharm. 2012;435(2):124–30. doi:10.1016/j.ijpharm.2012.05.070.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Nahata MC, Allen LV. Extemporaneous drug formulations. Clin Ther. 2008;30(11):2112–9. doi:10.1016/j.clinthera.2008.11.020.

    Article  PubMed  Google Scholar 

  4. 4.

    Preis M, Pein M, Breitkreutz J. Development of a taste-masked orodispersible film containing dimenhydrinate. Pharmaceutics. 2012;4(4):551–62. doi:10.3390/pharmaceutics4040551.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Stoltenberg I, Breitkreutz J. Orally disintegrating mini-tablets (ODMTs)—a novel solid oral dosage form for paediatric use. Eur J Pharm Biopharm. 2011;78(3):462–9. doi:10.1016/j.ejpb.2011.02.005.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Klingmann V, Spomer N, Lerch C, Stoltenberg I, Frömke C, Bosse HM, et al. Favorable acceptance of mini-tablets compared with syrup: a randomized controlled trial in infants and preschool children. J Pediatr. 2013;163(6):1728–32. doi:10.1016/j.jpeds.2013.07.014.

    Article  PubMed  Google Scholar 

  7. 7.

    Buanz AB, Belaunde CC, Soutari N, Tuleu C, Gul MO, Gaisford S. Ink-jet printing versus solvent casting to prepare oral films: effect on mechanical properties and physical stability. Int J Pharm. 2015;494(2):611–8. doi:10.1016/j.ijpharm.2014.12.032.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Voura C, Gruber MM, Schroedl N, Strohmeier D, Eitzinger B, Bauer W, et al. Printable medicines: a microdosing device for producing personalised medicines. Pharm Technol Eur. 2011;23(1):32–6.

    CAS  Google Scholar 

  9. 9.

    Preis M, Breitkreutz J, Sandler N. Perspective: concepts of printing technologies for oral film formulations. Int J Pharm. 2015;494(2):578–84. doi:10.1016/j.ijpharm.2015.02.032.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Genina N, Janßen EM, Breitenbach A, Breitkreutz J, Sandler N. Evaluation of different substrates for inkjet printing of rasagiline mesylate. Eur J Pharm Biopharm. 2013;85(3):1075–83. doi:10.1016/j.ejpb.2013.03.017.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Raijada D, Genina N, Fors D, Wisaeus E, Peltonen J, Rantanen J, et al. A step toward development of printable dosage forms for poorly soluble drugs. J Pharm Sci. 2013;102(10):3694–704. doi:10.1002/jps.23678.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Wickström H, Palo M, Rijckaert K, Kolakovic R, Nyman JO, Määttänen A, et al. Improvement of dissolution rate of indomethacin by inkjet printing. Eur J Pharm Biopharm. 2015;75:91–100. doi:10.1016/j.ejps.2015.03.009.

    Google Scholar 

  13. 13.

    Genina N, Fors D, Vakili H, Ihalainen P, Pohjala L, Ehlers H, et al. Tailoring controlled-release oral dosage forms by combining inkjet and flexographic printing techniques. Eur J Pharm Sci. 2012;47(3):615–23. doi:10.1016/j.ejps.2012.07.020.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    National Institutes of Health (NIH). Nutrient recommendations: dietary reference intakes (DRI) Accessed 12 Aug 2016.

  15. 15.

    Kolakovic R, Viitala T, Ihalainen P, Genina N, Peltonen J, Sandler N. Printing technologies in fabrication of drug delivery systems. Expert Opin Drug Deliv. 2013;10(12):1711–23. doi:10.1517/17425247.2013.859134.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Alomari M, Mohamed FH, Basit AW, Gaisford S. Personalised dosing: printing a dose of one’s own medicine. Int J Pharm. 2015;494(2):568–77. doi:10.1016/j.ijpharm.2014.12.006.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Vakili H, Kolakovic R, Genina N, Marmion M, Salo H, Ihalainen P, et al. Hyperspectral imaging in quality control of inkjet printed personalised dosage forms. Int J Pharm. 2015;483(1):244–9. doi:10.1016/j.ijpharm.2014.12.034.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Hammes F, Hille T, Kissel T. Reflectance infrared spectroscopy for in-line monitoring of nicotine during a coating process for an oral thin film. J Pharm Biomed Anal. 2014;89:176–82. doi:10.1016/j.jpba.2013.10.047.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Ayaz EA, Altintas SH, Turgut S. Effects of cigarette smoke and denture cleaners on the surface roughness and color stability of different denture teeth. J Prosthet Dent. 2014;112(2):241–8. doi:10.1016/j.prosdent.2014.01.027.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Rossel RV, Minasny B, Roudier P, McBratney AB. Colour space models for soil science. Geoderma. 2006;133(3):320–37. doi:10.1016/j.geoderma.2005.07.017.

    Article  Google Scholar 

  21. 21.

    Trinderup CH, Dahl A, Jensen K, Carstensen JM, Conradsen K. Comparison of a multispectral vision system and a colorimeter for the assessment of meat color. Meat Sci. 2015;102:1–7. doi:10.1016/j.meatsci.2014.11.012.

    Article  PubMed  Google Scholar 

  22. 22.

    Yagiz Y, Balaban MO, Kristinsson HG, Welt BA, Marshall MR. Comparison of Minolta colorimeter and machine vision system in measuring colour of irradiated Atlantic salmon. J Sci Food Agric. 2009;89(4):728–30. doi:10.1002/jsfa.3467.

    CAS  Article  Google Scholar 

  23. 23.

    Wu D, Sun DW. Colour measurements by computer vision for food quality control—a review. Trends Food Sci Technol. 2013;29(1):5–20. doi:10.1016/j.tifs.2012.08.004.

    Article  Google Scholar 

  24. 24.

    Facundo HV, Gurak PD, Mercadante AZ, Lajolo FM, Cordenunsi BR. Storage at low temperature differentially affects the colour and carotenoid composition of two cultivars of banana. Food Chem. 2015;170:102–9. doi:10.1016/j.foodchem.2014.08.069.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Green MD, Hostetler DM, Nettey H, Swamidoss I, Ranieri N, Newton PN. Integration of novel low-cost colorimetric, laser photometric, and visual fluorescent techniques for rapid identification of falsified medicines in resource-poor areas: application to artemether–lumefantrine. Am J Trop Med Hyg. 2015;92(6 Suppl):8–16. doi:10.4269/ajtmh.14-0832.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Steele G. Preformulation as an aid to product design in early drug development. In: Gibson M, editor. Pharmaceutical preformulation and formulation. 2nd ed. New York: Informa Healtcare USA, Inc; 2009. p. 206–7.

    Google Scholar 

  27. 27.

    Bhugra D, Ventriglio A, Till A, Malhi G. Colour, culture and placebo response. Int J Soc Psychiatry. 2015;61(6):615–7. doi:10.1177/0020764015591492.

    Article  PubMed  Google Scholar 

  28. 28.

    Leon K, Mery D, Pedreschi F, Leon J. Color measurement in L∗ a∗ b∗ units from RGB digital images. Food Res Int. 2006;39(10):1084–91. doi:10.1016/j.foodres.2006.03.006.

    Article  Google Scholar 

  29. 29.

    Tung FF, Goldstein GR, Jang S, Hittelman E. The repeatability of an intraoral dental colorimeter. J Prosthet Dent. 2002;88(6):585–90. doi:10.1067/mpr.2002.129803.

    Article  PubMed  Google Scholar 

  30. 30.

    CLM-194 User Guide, Digital handheld colorimeter, Eoptis, Rev. 1.04-03/2014.

  31. 31.

    Yam KL, Papadakis SE. A simple digital imaging method for measuring and analyzing color of food surfaces. J Food Eng. 2004;61(1):137–42. doi:10.1016/S0260-8774(03)00195-X.

    Article  Google Scholar 

  32. 32.

    Sandler N, Määttänen A, Ihalainen P, Kronberg L, Meierjohann A, Viitala T, et al. Inkjet printing of drug substances and use of porous substrates-towards individualized dosing. J Pharm Sci. 2011;100(8):3386–95. doi:10.1002/jps.22526.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Genina N, Fors D, Palo M, Peltonen J, Sandler N. Behavior of printable formulations of loperamide and caffeine on different substrates—effect of print density in inkjet printing. Int J Pharm. 2013;453(2):488–97. doi:10.1016/j.ijpharm.2013.06.003.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Buanz AB, Saunders MH, Basit AW, Gaisford S. Preparation of personalized-dose salbutamol sulphate oral films with thermal ink-jet printing. Pharm Res. 2011;28(10):2386–92. doi:10.1007/s11095-011-0450-5.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Sheraz MA, Kazi SH, Ahmed S, Anwar Z, Ahmad I. Photo, thermal and chemical degradation of riboflavin. Aubé J, ed. Beilstein J Org Chem. 2014;10:1999–2012. doi:10.3762/bjoc.10.208.

  36. 36.

    Hudd A. Inkjet printing technologies. In: Magdassi S, editor. Chemistry of inkjet inks. Singapore: WSPC; 2009. p. 7.

    Google Scholar 

  37. 37.

    Meléndez PA, Kane KM, Ashvar CS, Albrecht M, Smith PA. Thermal inkjet application in the preparation of oral dosage forms: dispensing of prednisolone solutions and polymorphic characterization by solid‐state spectroscopic techniques. J Pharm Sci. 2008;97(7):2619–36. doi:10.1002/jps.21189.

    Article  PubMed  Google Scholar 

  38. 38.

    Sue-Chu M, Kristensen S, Tønnesen HH. Influence of lag-time between light exposure and color evaluation of riboflavin in the solid state. Pharmazie. 2008;63(7):545–6. doi:10.1691/ph.2008.8070.

    CAS  PubMed  Google Scholar 

  39. 39.

    Stark G, Fawcett JP, Tucker IG, Weatherall IL. Instrumental evaluation of color of solid dosage forms during stability testing. Int J Pharm. 1996;143(1):93–100. doi:10.1016/S0378-5173(96)04691-1.

    CAS  Article  Google Scholar 

  40. 40.

    Allam KV, Kumar GP. Colorants—the cosmetics for the pharmaceutical dosage forms. Int J Pharm Pharm Sci. 2011;3(3):13–21.

    Google Scholar 

  41. 41.

    Takala M, Helkiö H, Sundholm J, Genina N, Kiviluoma P, Widmaier T, Sandler N, Kuosmanen P. Ink-jet printing of pharmaceuticals. In: Proceedings of the 8th International DAAAM Baltic Conference 2012 Apr 19.

  42. 42.

    Sorak D, Herberholz L, Iwascek S, Altinpinar S, Pfeifer F, Siesler HW. New developments and applications of handheld Raman, mid-infrared, and near-infrared spectrometers. Appl Spectrosc Rev. 2012;47(2):83–115. doi:10.1080/05704928.2011.625748.

    Article  Google Scholar 

  43. 43.

    Hajjou M, Qin Y, Bradby S, Bempong D, Lukulay P. Assessment of the performance of a handheld Raman device for potential use as a screening tool in evaluating medicines quality. J Pharm Biomed Anal. 2013;74:47–55. doi:10.1016/j.jpba.2012.09.016.

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Preis M and Sandler N. Printing technologies and tailored dosing. Hosp Healthc. 2016;in press.

Download references


The funding from Tor, Joe och Pentti Borg Fond is greatly acknowledged. Emrah Yildir is thanked for showing the Lorentzen & Wettre micrometer device used for substrate thickness measurements.

Author information



Corresponding author

Correspondence to Henrika Wickström.

Additional information

Guest Editors: Maren Preis and Jörg Breitkreutz

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wickström, H., Nyman, J.O., Indola, M. et al. Colorimetry as Quality Control Tool for Individual Inkjet-Printed Pediatric Formulations. AAPS PharmSciTech 18, 293–302 (2017).

Download citation


  • fixed-dose combinations
  • handheld colorimeter
  • inkjet printing
  • pediatric medicine
  • quality control