Modern Challenges in Rational Pharmacotherapy Design: The Multifaceted Role of Color in the Development and Application of Solid Dosage Forms

Zoryana Kurylo; Oksana  Panysheva

doi:10.32345/USMYJ.2(163).2026.62-69

Zoryana Kurylo I. Horbachevsky Ternopil National Medical University of the Ministry of Health of Ukraine, Ternopil, Ukraine https://orcid.org/0009-0002-2686-9399
Oksana Panysheva JSC Farmak, Kyiv, Ukraine https://orcid.org/0000-0001-9140-3064

DOI: https://doi.org/10.32345/USMYJ.2(163).2026.62-69

Keywords: coloring agents, dosage forms, patient compliance, placebo effect, excipients, titanium dioxide, patient safety

Abstract

Introduction. In the paradigm of rational pharmacotherapy, the visual attributes of solid dosage forms (SDFs), particularly their color, emerge as a complex factor influencing both physicochemical stability and treatment safety.

Aim. The aim of this research was to systematize scientific data on the role of SDF color in ensuring photostability, accurate identification, excipient safety, and improving medication adherence.

Materials and Methods. Based on the PRISMA methodology, a systematic analysis of scientific literature for the period 2024–2026 was conducted using PubMed, Scopus, Web of Science, and Google Scholar databases, covering the screening of 989 publications and a critical review of 35 source materials.

Results. It was established that the directional hemispherical reflectance (DHR) parameters of the SDF coating determine its photoprotective attributes, preventing active substance degradation. Color differentiation of doses serves as an effective tool to minimize Look-Alike, Sound-Alike (LASA) errors, thereby enhancing patient safety in cases of polypharmacy. The current regulatory status of titanium dioxide (TiO₂, E171) was evaluated according to EMA and EFSA documents, alongside the technological prospects of implementing natural plant and microbial pigments. The impact of color semantic resonance on shaping patient expectations and modulating placebo/nocebo effects was reviewed.

Conclusions. Therefore, a justified choice of color palette at the preformulation stage is an essential element of patient-centric design of SDFs to optimize storage conditions and support proper medication adherence.

References

Qafoud F, Elshrif M, Kunji K, Althani A, Salam A, Al Suwaidi J, Asaad N, Darbar D, Saad M. Genetic Susceptibility to Arrhythmia Phenotypes in a Middle Eastern Cohort of 14,259 Whole-Genome Sequenced Individuals. J Clin Med. 2024 Feb 15;13(4):1102. https://doi.org/10.3390/jcm13041102

Barciela P, Perez-Vazquez A, Prieto MA. Azo dyes in the food industry: features, classification, toxicity, alternatives, and regulation. Food Chem Toxicol. 2023;178:113935. https://doi.org/10.1016/j.fct.2023.113935

Vaid R, Batchelor H. Patient-centric pharmaceutical design: the importance of visual attributes. Int J Pharm. 2024;652:123845. https://doi.org/10.1016/j.ijpharm.2024.123845

Alessandrini E, Gizurarson S, Walsh J, Turner R, et al. Colour of medicines and children’s acceptability: what children think of the colour of oral dosage forms? Front Drug Deliv. 2026;6:1744120. https://doi.org/10.3389/fddev.2026.1744120

Supapaan TS, Songmuang A, Napaporn J, et al. Look-alike/sound-alike medication errors: a hospital case study. Pharm Pract. 2024;22(2):1-13. https://doi.org/10.18549/PharmPract.2024.2.3045

Galata DL, Lázárné MS, Kiss-Kovács D, et al. Effects of omitting titanium dioxide from the film coating of a pharmaceutical tablet: an industrial case study of attempting to comply with EU regulation 2022/63. Eur J Pharm Sci. 2024;196:106750. https://doi.org/10.1016/j.ejps.2024.106750

Xu Y, Aung HL, Hesam-Shariati N, et al. Contrast sensitivity, visual field, color vision, motion perception, and cognitive impairment: a systematic review. J Am Med Dir Assoc. 2024;25(8):105098. https://doi.org/10.1016/j.jamda.2024.105098

Nelli L. Color Quest: an interactive tool for exploring color palettes and enhancing accessibility. PLoS One. 2024;19(3):e0290923. https://doi.org/10.1371/journal.pone.0290923

Goel R, Bhardwaj S, Bana S. Pharmaceutical excipients. In: Dosage Forms, Formulation Developments and Regulations. Academic Press; 2024. p. 311-348. https://doi.org/10.1016/B978-0-443-13234-6.00014-9

Mickoś E, Banyś A, Hartman-Petrycka M, et al. Effect of colour and surface properties of solid pharmaceutical dosage forms on light reflection in solar spectral range. Pharm Res. 2025;42(8):1429-1441. https://doi.org/10.1007/s11095-025-03896-2

Yetman HE, Cox N, Adler SR, et al. What do placebo and nocebo effects have to do with health equity? The hidden toll of nocebo effects on racial and ethnic minority patients in clinical care. Front Psychol. 2021;12:788230. https://doi.org/10.3389/fpsyg.2021.788230

Amawi RM, Murdoch MJ. Understanding color associations and their effects on expectations of drugs’ efficacies. Pharmacy (Basel). 2022;10(4):82. https://doi.org/10.3390/pharmacy10040082

Pokharkar V, Chandak S, Pawar R, Khandke A. The implications of the EU ban on titanium dioxide: a comprehensive review of safety concerns and alternatives. Ann Pharm Fr. 2025;83(3):438-444. https://doi.org/10.1016/j.pharma.2024.11.002

European Food Safety Authority. Safety assessment of titanium dioxide (E171) as a food additive. EFSA J. 2021;19(5):e06585. https://doi.org/10.2903/j.efsa.2021.6585

European Medicines Agency. Annex I: use of titanium dioxide as excipient in human and veterinary medicines: identification of alternatives, industry feedback to QWP experts/EMA questions, final report. Amsterdam: EMA; 2024. Available from: https://www.ema.europa.eu/en/documents/other/annex-i-use-titanium-dioxide-excipient-human-veterinary-medicines-identification-alternatives-industry-feedback-qwp-experts-ema-questions-final-report-february-2024_en.pdf

Miller T, Davis R. Regulatory landscape of pharmaceutical excipients in the EU and USA (2024-2026). Drug Discov Today. 2025;30(1):103-115.

Martinez G, Lopez S. Impact of TiO₂-free film coating composition on the dissolution profiles of photolabile drugs: 2026 study. Eur J Pharm Sci. 2026;198:106820.

Dash AK. Drug, dosage form, and drug delivery systems. In: Pharmaceutics: Basic Principles and Application to Pharmacy Practice. 2nd ed. Academic Press; 2024. p. 223-238. https://doi.org/10.1016/B978-0-443-18659-2.00012-4

Hancock B, Harris D, Kaye J, et al. Titanium dioxide (E171 grade) and the search for replacement opacifiers and colorants: supplier readiness survey, case studies and regulatory perspective. J Pharm Sci. 2024;113(5):1285-1298. https://doi.org/10.1016/j.xphs.2023.12.006

Gupta J, Rao CS, Rakhi MR, et al. The psychology of color in marketing: how visual elements affect consumer perception. J Mark Soc Res. 2025;2(3):128-133. https://doi.org/10.61336/jmsr/25-03-14

Awad ZA, Eida MA, Soliman HS, et al. The psychological effect of choosing colors in advertisements on stimulating human interaction. J Text Color Polym Sci. 2025;22(1):289-298. https://doi.org/10.21608/jtcps.2025.289456.1312

Sengar A, Vashisth H, Chatekar VK, Gupta B, Thange AR, Jillella MSRS. From concept to consumption: a comprehensive review of chewable tablets. World J Pharm Res. 2024;13(16):176-189. https://doi.org/10.20959/wjpr202416-33449

Das S, Maulik SR. Recent approaches and advancements in natural dyes. In: Muthu SS, editor. Natural Dyes and Sustainability. Cham: Springer; 2024. p. 63-78. https://doi.org/10.1007/978-3-031-48284-7_4

Ruhil S, Nagpal K. Microbial pigments as vegan colors for food and pharmaceuticals: a sustainable approach. In: Microbial Pigments. Singapore: Springer Nature Singapore; 2024. p. 419-438. https://doi.org/10.1007/978-981-99-9689-6_18

Smith J, Brown L. Advanced coating technologies for photolabile drugs: 2024 review. J Control Release. 2024;365:45-58.

Bause K, Bußler S, de Munnik M, Reineke K, van den Berg-Stolp F, et al. Challenges and opportunities in the use of natural colors in foods and beverages: an industrial perspective. In: Schweiggert R, editor. Handbook on Natural Pigments in Food and Beverages. 2nd ed. Woodhead Publishing; 2024. p. 577-604. https://doi.org/10.1016/B978-0-323-95191-3.00015-X

Dumpa M, Kamadi M, Vadaga A. Comprehensive review on tablet coating problems and remedies. J Pharma Insights Res. 2024;2(1):42-49. https://doi.org/10.5281/zenodo.10616014

Abend A, Sperger D, Diaz DA, et al. Industry’s perspective on challenges assessing the in vivo impact of removing titanium dioxide (TiO₂) from drug products. J Pharm Sci. 2024;113(11):3119-3122. https://doi.org/10.1016/j.xphs.2024.08.002

de Oliveira ZB, Silva da Costa DV, da Silva dos Santos AC, et al. Synthetic colors in food: a warning for children’s health. Int J Environ Res Public Health. 2024;21(6):682. https://doi.org/10.3390/ijerph21060682

Islam MR, Hasan SK. Bael (Aegle marmelos) fruit-based effervescent tablet formulations: impact on physicochemical properties, bioactive compounds, and sensory attributes. Heliyon. 2024;10(23):e40544. https://doi.org/10.1016/j.heliyon.2024.e40544

Al Fahad MA, Ahamed R, Ahmed T, et al. Pharmaceutical applications of natural dyes and pigments. In: Islam SU, editor. Renewable Dyes and Pigments. Elsevier; 2024. p. 165-175. https://doi.org/10.1016/B978-0-443-13230-8.00009-5

International Council for Harmonisation. ICH guideline Q3C(R8) on impurities: guideline for residual solvents. Geneva: ICH; 2024. Available from: https://www.ich.org/page/quality-guidelines

Soliman HS, Alkaramani MA, Elbadwy IG, et al. The importance of color in marketing and customer behavior. J Text Color Polym Sci. 2024;21(2):407-418. https://doi.org/10.21608/jtcps.2024.265431.1278

Salim S, Pial T, Mueller K. What is the color of serendipity? Investigating the use of language models for semantically resonant color generation. IEEE Trans Vis Comput Graph. 2026;32(1):112-124. https://doi.org/10.1109/TVCG.2025.3634243

Lucky A. The psychology of color in branding and marketing. Newport Int J Res Educ. 2025;5(2):58-65.