Advances in the use of instrumental measurement of colour in the development, production and quality control of drugs, medicinal preparations and pharmaceutical auxiliary substances I 

Authors: Jan Šubert;  Jozef Čižmárik
Authors‘ workplace: Univerzita Komenského v Bratislave, Farmaceutická fakulta, Katedra farmaceutickej chémie, Slovenská republika
Published in: Čes. slov. Farm., 2013; 62, 65-70
Category: Review Articles


Colour is one of the important indices of the quality of drugs, medicinal preparations and pharmaceutical auxiliary substances. The paper summarizes the development and use of instrumental measurement of colour in pharmacy in recent ten years focusing on the drugs of synthetic origin and pharmaceutical auxiliary substances including their control.

Key words:
measurement of colour • colour spaces • drugs and medicinal preparations • auxiliary substances • analytical applications


1. Šubert J., Čižmárik J. Application of instrumental colour measurement in development and quality control of drugs and pharmaceutical excipients. Pharmazie 2008; 63, 331–336.

2. Melgosa M., Huertas R., Berns R. S. Relative significance of the terms in the CIEDE2000 and CIE94 color-difference formulas. J. Opt. Soc. Am. A 2004; 21, 2269–2275.

3. Melgosa M., Huertas R., Berns R. S. Performance of recent advanced color- difference formulas using the standardized residual sum of squares index. J. Opt. Soc. Am. A 2004; 25, 1828–1834.

4. García-Monlleó R. M., Rivas M. J., Huertas R., Melgosa M. Disinfecting solutions for soft contact lenses using different color indicators. Optom. Vis. Sci. 2006; 83, 160–165.

5. Paravina R. D., Kimura M., Powers J. M. Evaluation of polymerization- dependent changes in color and translucency of resin composites using two formulae. Odontology 2005; 93, 46–51.

6. Pérez M., Saleh A., Yebra A., Pulgar R. Study of the variation between CIELAB ∆E* and CIEDE2000 color-differences of resin composites. Dent. Mater. J. 2007; 26, 21–28.

7. Wee A. G., Lindsey D. T., Shroyer K. M, Johnston W. M. Use of a porcelain color discrimination test to evaluate color difference formulas. J. Prosthet. Dent. 2007; 98, 101–109.

8. Nippolainen E., Ervasti T., Fauch L., Miridonov S. V., Ketolainen J., Kamshilin A. A. Fast noncontact measurements of tablet dye concentration. Opt. Express 2010; 18, 15624–15634.

9. Gao L., Ren W., Li F., Cheng H. M. Total color difference for rapid and accurate identification of graphene. ACS Nano 2008; 2, 1625–1633.

10. Lakio S., Heinämäki J., Yliruusi J. Colorful drying. AAPS PharmSciTech. 2010; 11, (1), 46–53. http://www.ncbi.nlm. (24. 1. 2013).

11. Derganc J., Likar B., Bernard R., Tomaževič D., Pernuš F. Real-time automated visual inspection of color tablets in pharmaceutical blisters. Real-Time Imaging 2003; 9, 113–124.

12. Lee Y. B., Park U., Jain A. K., Lee S. W. Pill-ID: Matching and retrieval of drug pill images. Pattern Recognit. Lett. 2012; 33, 904–910.

13. Jung C.R, Ortiz R.S, Limberger R., Mayorga P. A new methodology for detection of counterfeit Viagra® and Cialis® tablets by image processing and statistical analysis. Forensic Sci. Int. 2012; 216, 92–96.

14. Wang J., Zeng L., Zang Q., Gong Q., Li B., Zhang X., Chu X., Zhang P., Zhao Y., Xiao X. Colorimetric grading scale can promote the standardization of experiential and sensory evaluation in quality control of traditional Chinese medicines. PLoS ONE 2012; 7, (11): e48887, doi: 10.1371/journal.pone.0048887. http// (24. 1. 2013).

15. Cantrell K., Erenas M. M., de Orbe-Payá I., Capitán-Valvey L. F. Use of the hue parameter of the hue, saturation, value color space as a quantitative analytical parameter for bitonal optical sensors. Anal. Chem. 2010; 82, 531–542.

16. Vulič J. J., Vračar L. O., Šumič Z. M. Chemical characteristics of cultivated elderberry fruit. APTEFF 2008; 39, 85–90.

17. Moyano M. J., Meléndez-Martínez A. J., Alba J., Heredia F. J. A comprehensive study on the colour of virgin olive oils and its relationship with their chlorophylls and carotenoids indexes (II): CIELUV and CIELAB uniform colour spaces. Food Res. Int. 2008; 41, 513–521.

18. Singh B., Parwate D. V., Shukla S. K. Radiosterilization of fluoroquinolones and cephalosporins: Assessment of radiation damage on antibiotics by changes in optical property and colorimetric parameters. AAPS PharmSciTech. 2009; 10, 34–43. http://www.ncbi. nlm.nih.govpmc/articles/PMC2663667 (24. 1. 2013).

19. Apyari V.V., Dmitrienko S. G., Zolotov Y. A. Analytical possibilities of digital colorimetry: Determination of nitrite using polyurethane foam. Moscow Univ. Chem. Bull. 2011; 66, 36–42.

20. Oram P. D., Strine J. Color measurement of a solid active pharmaceutical ingredient as an aid to identifying key process parameters. J. Pharm. Biomed. Anal. 2006; 40, 1021–1024.

21. Zhou L., Vogt F. G., Overstreet P.-A., Dougherty J. T., Clawson J. S., Kord A. S. A systematic method development strategy for quantitative color measurement in drug substances, starting materials, and synthetic intermediates. J. Pharm. Innov. 2011; 6, 217–231.

22. Hayauchi Y. A precise colour determination method for tablets – an application of instrumental colour measurement in the pharmaceutical development. Pharmeur. Sci. Notes 2005; (1), 21–26.

23. Nkansah P., Wu S. J., Lukulay P., Taylor G., Hsieh W. Y., Spong B., Culver M. Using colorimetric techniques and capability analysis to develop standard placebo tablets for clinical studies. J. Pharm. Innov. 2009; 4, 71–80.

24. Moribe K., Kinoshita R., Higashi K., Tozuka Y., Yamamoto K. Coloration phenomenon of mefenamic acid in mesoporous silica FSM-16. Chem. Pharm. Bull. 2010; 58, 214–218.

25. Tanabe S., Higashi K., Umino M., Limwikrant W., Yamamoto K. Yellow coloration phenomena of incorporated indomethacin into folden sheet mesoporous materials. Int. J. Pharm. 2012; 429, 38–45.

26. Teraoka R., Otsuka M., Matsuda Y. Evaluation of photostability of solid-state nicardipine hydrochloride polymorphs by using Fourier-transformed reflection-absorption infrared spectroscopy – effect of grinding on the photostability of crystal form. Int. J. Pharm. 2004; 286: 1–8.

27. Kojima T., Onoue S., Katoh F., Teraoka R., Matsuda Y., Kitagawa S., Tsuhako M. Effect of spectroscopic properties on photostability of tamoxifen citrate polymorphs. Int. J. Pharm. 2007; 336, 346–351.

28. Onoue S., Igarashi N., Yamauchi Y., Murase N., Zhou Y., Kojima T., Yamada S., Tsuda Y. In vitro phototoxicity of dihydropyridine derivatives: A photochemical and photobiological study. Eur. J. Pharm. Sci. 2008; 33, 262–270.

29. Sue-Chu M., Kristensen S., Tønnesen H. H. Influence of lag-time between light exposure and color evaluation of riboflavin in the solid state. Pharmazie 2008; 63, 545–546.

30. Sue-Chu M., Kristensen S., Tønnesen H. H. Photoinduced color changes in two different qualities of riboflavin in the solid state and in various tablet formulations. Photoreactivity of biologically active compounds. XX. Pharmazie 2009; 64, 428–435.

31. Tønnesen H. H., Brunsvik A., Løseth K., Bergh K., Gederaas O. A. Photoreactivity of biologically active compounds. XVIII. Photostability of ofloxacin in the solid state and in a tablet formulation. Pharmazie 2007; 62, 105–111.

32. Hegge A. B., Andersen T., Melvik J. E., Kristensen S., Tønnesen H. H. Evaluation of novel alginate foams as drug delivery systems in antimicrobial photodynamic therapy (aPDT) of infected wounds—an in vitro study: Studies on curcumin and curcuminoides XL. J. Pharm. Sci. 2010; 99, 3499–3515.

33. Kakinoki K., Yamane K., Yamamoto M., Teraoka R., Sugimoto I., Matsuda Y. Effect of titanium dioxide on photostability of solid-state mequitazine. Chem. Pharm. Bull. 2005; 53, 1092–1096.

34. Ramadan A., El-Massik M., El-Khordagui L., Daabis N., Hammouda Y. Surface treatment: A potential approach for enhancement of solid-state photostability. Int. J. Pharm. 2006; 307, 141–149.

35. Singh B. K., Parwate D.V., Dassarma I. B., Shukla S. K. Radiation sterilization of fluoroquinolones in solid state: Investigation of effect of gamma radiation and electron beam. Appl. Radiat. Isot. 2010; 68, 1627–1635.

36. Gavrilov A. S., Zalukina I. V., Koneva L. A., Bakharev V. P., Petrov A. Yu. Rapid evaluation of tablet color. Pharm. Chem. J. 2003; 37, 273–276.

37. Gavrilov A. S., Guseľnikova E. V., Petrov A. Yu. Optimization of the composition and wet granulation technology of drotaverine hydrochloride tablets. Pharm. Chem. J. 2005; 39, 274–277.

38. Rhee Y. S., Park C. W., Shin Y. S., Lee K. H., Park E. S. Application of instrumental evaluation of color for the pre-formulation and formulation of rabeprazole. Int. J. Pharm. 2008; 350, 122–129.

39. Matsumoto R., Kawakami K., Aoki S. Impact of compression pressure on tablet appearance. Int. J. Pham. 2007; 341, 44–49.

40. Siddiqui A., Nazzal S. Measurement of surface color as an expedient QC method for the detection of deviations in tablet hardness. Int. J. Pharm. 2007; 341, 173–180.

41. Yamazaki N., Taya K., Shimokawa K., Ishii F. The most appropriate storage method in unit-dose package and correlation between color change and decomposition rate of aspirin tablets. Int. J. Pharm. 2010; 396, 105–110.

42. Heng P. W. S., Chan L. W., Tang E. S. K. Use of swirling airflow to enhance coating performance of bottom spray fluid bed coaters. Int. J. Pharm. 2006; 327, 26–35.

43. Cunningham C., Hansell J., Nuneviller III F., Rajabi-Siahboomi A. R. Evaluation of recent advances in continuous film coating processes. Drug Dev. Ind. Pharm. 2010; 36, 227–233.

44. Kawata K., Hanawa T., Endo N., Suzuki M., Oguchi T. Formulation study on retinoic acid gel composed of iota-carrageenan, polyethylene oxide and Emulgen® 408. Chem. Pharm. Bull. 2012; 60, 825–830.

45. Šubert J., Farsa O., Cieslarová M. Efficiency of stabilization of low level of coloration of Castellani´s paint without fuchsine with disodium edetate. Pharmazie 2006; 61, 1049–1050.

46. Gámiz E., Melgosa M., Sánchez-Maranón M., Martín-García J. M., Delgado R. Relationships between chemico-mineralogical composition and color properties in selected natural and calcined Spanish kaolins. Appl. Clay Sci. 2005; 28, 269–282.

47. Nemţtanu M. R., Minea R., Kahraman K., Koksel H., Ng P. K. W., Popescu M. I., Mitru E. Electron beam technology for modifying the functional properties of maize starch. Nucl. Instrum. Methods Phys. Res. A 2007; 580, 795–798.

48. Kuan Y. H., Bhat R., Senan C., Williams P. A., Karim A. A. Effect of ultraviolet irradiation on the physicochemical and functional properties of gum arabic. J. Agric. Food Chem. 2009; 57, 9154–9159.

49. Moyano M. J., Meléndez-Martínez A. J., Alba J., Heredia F. J. A comprehensive study on the colour of virgin olive oils and its relationship with their chlorophylls and carotenoids indexes (I): CIEXYZ non-uniform colour space. Food Res. Int. 2008; 41, 505–512.

50. Escolar D., Haro M. R., Ayuso J. The color space of foods: Virgin olive oil. J. Agric. Food Chem. 2007; 55, 2085–2093.

51. Ceballos C., Moyano M. J., Vicario I. M., Alba J., Heredia F. J. Chromatic evolution of virgin olive oils submitted to an accelerated oxidation test. J. Am. Oil Chem. Soc. 2003; 80: 257–262.

52. Mapari S. A. S., Meyer A. S., Thrane U. Colorimetric characterization for comparative analysis of fungal pigments and natural food colorants. J. Agric. Food Chem. 2006; 54, 7027–7035.

53. Meléndez-Martínez A. J., Britton G., Vicario I. M., Heredia F. J. Relationship between the colour and the chemical structure of carotenoid pigments. Food Chem. 2007; 101, 1145–1150.

54. Ali S. L., Castle P. Measurement of colour of liquids. Pharmeuropa 2003; 15, 262–266.

55. Šubert J., Farsa O., Gajdošová Z. Properties of colour reference solutions of the European Pharmacopoea in CIE L*a*b* colour space. Pharmazie 2006; 61, 1047–1048.

56. Šubert J., Farsa O., Gajdošová Z. Teorie a praxe lékopisné kontroly jakosti léčiv a pomocných látek VI. Stabilita porovnávacích barevných roztoků ČL 2002. Čes. slov. Farm. 2006; 55, 189–191.

57. Singh B. K., Parwate D. V., Shukla S. K. Rapid color test identification system for screening of counterfeit fluoroquinolone. E-J. Chem. 2009; 6, 377–384, doi:10.1155/2009/870286.

(24. 1. 2013).

58. Gámiz E., Párraga J., Sánchez-Maranón M., Melgosa M., Fernández-Gonzales M. V., Delgado R. Is the Pharmacopoeia test a good estimator of the organic impurities in kaolin? Appl. Clay Sci 2011; 51, 431–437.

59. Ivanov V. M., Adamova E. M., Figurovskaya V. B. Alizarin Red S as a colored agent for the extraction-photometric and color measurement determination of some local anesthetic organic compound. J. Anal. Chem. 2010; 65, 934–942.

60. Ivanov V. M., Adamova E. M., Figurovskaya V. B. Sorption-spectrophotometry and chromaticity determination of some organic bases used in local anesthesia using Alizarin Red C. J. Anal. Chem. 2012; 67, 485–492.

61. Shimada T., Ookubo K., Komuro N., Shimizu T., Uehara N. Blue-to-red chromatic sensor composed of gold nanoparticles conjugated with thermoresponsive copolymer for thiol sensing. Langmuir 2007; 23, 11225–11232.

62. Uehara N., Ookubo K., Shimizu T. Colorimetric assay of glutathione based on the spontaneous disassembly of aggregated gold nanocomposites conjugated with water-soluble polymer. Langmuir 2010; 26, 6818–6825.

63. Kochelaeva G. A., Ivanov V. M., Simonova E. N. Pyrocatechol violet in new optical methods for determining aluminium. J. Anal. Chem. 2008; 63, 342–348.

64. Shishkin Y. L., Dmitrienko S. G., Medvedeva O. M., Badakova S. A., Pyatkova L. N. Use of a scanner and digital image-processing software for the quantification of adsorbed substances. J. Anal. Chem. 2004; 59, 102–106.

65. Choodum A., Nic Daied N. Rapid and semi-quantitative presumptive tests for opiate drugs. Talanta 2011; 86, 284–292.

66. Choodum A., Nic Daied N. Digital image-based colourimetric tests for amphetamine and methylamphetamine. Drug Test. Analysis 2011; 3, 277–282.

67. Abbaspour A., Khajehzadeh A., Noori A. A simple and selective sensor for the determination of ascorbic acid in vitamin C tablets based on paptode. Anal. Sci. 2008; 24, 721–725.

68. Anwar J., Salman M., Shafique U., Zaman W., Dar A., Anzano M. J. Micro-determination of iron in pharmaceutical preparations by image scanning and computation quantification. Curr. Med. Chem. 2010; 17, 4424–4426.

69. Tavallali H., Nike E. A simple and selective sensor for determination of iron(II) in drug samples based on paptode. Asian J. Biochem. Pharm. Res. 2011; 1, 91–97.

70. Sharma R. D., Joshi S., Amlathe S. Paper optode: a new optical analytical tool for determination of HG (II) and its application for removal from aqueous samples. Asian J. Pharm. Biol. Res. 2012; 2, 161–168.

71. Baghel A., Amlathe S. Development of paptodes for determination of hydrazine in water and its application in biological samples and pharmaceutical tablet. J. Chem. Pharm. Res. 2012; 4, 1546–1552. (24. 1. 2013).

72. Sharma R. D., Joshi S., Amlathe S. MATLAB assisted disponsable sensors for quantitative determination of arsenic, Anal. Methods 2011; 3, 452–456.

73. Abbaspour A., Norouz-Sarvestani F., Mirahmadi E. Development of non-enzymatic strip for simple and selective determination of urea in water and biological samples. J. Iran Chem. Soc. 2012; 9, 383–388.

74. Lyra W. S., Santos V. B., Dionízio A. G. G., Martins V. L., Almeida L. F., Gaião E. N., Diniz P. H. G. D., Silva E. C., Araújo M. C. U. Digital image-based flame emission spectrometry. Talanta 2009; 77, 1584–1589.

75. Lyra W. S., Sanchez F. A. C., Cunha F. A. S., Diniz P. H. G. D., Lemos S. G., Silva E. C., Araujo M. C. U. Indirect determination of sodium diclofenac, sodium dipyrone and calcium gluconate in injection drugs using digital image-based (webcam) flame emission spectrometric method. Anal. Methods 2011; 3, 1975–1980.

Pharmacy Clinical pharmacology
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account