Taste Masking Challenge of 155 Active Pharmaceutical Ingredients

Main Article Content

David A. Tisi Jeffrey H. Worthington

Abstract

Regulations in the US and EU require and incentivize the development of palatable, age-appropriate medicines for children. However, the taste masking challenge of new drug actives is generally unknown, making development of palatable drug products extremely difficult. To develop palatable drug products, formulation scientists first need to determine if the drug active is bitter, has an offensive aroma (malodor) or is burning as each perception requires a different formulation approach. This retrospective compilation of results of 155 taste assessment studies reveals diversity in aversive flavor attributes of active ingredients. Bitterness was the primary taste masking challenge for 65% of the drug actives. Aversive aromas (e.g., solvent, fishy, oxidized oil) were the second most common challenge, impacting 8% of drug actives. Approximately 5% had trigeminal irritation, and a smaller subset were sour or salty (4%). None were found to be sweet. Of note, 14% of drug actives were “bland” in flavor, with no measured aversive attributes. Complicating development, most actives (>90%) were found to have multiple aversive flavor attributes. These findings highlight the need to determine the aversive attributes early in clinical development (Phase 1) to guide dosage form selection and formulation design.

Keywords: Active pharmaceutical ingredient, sensory analysis, taste, flavor, taste masking, aversive flavor attribute, flavor profile

Article Details

How to Cite
TISI, David A.; WORTHINGTON, Jeffrey H.. Taste Masking Challenge of 155 Active Pharmaceutical Ingredients. Medical Research Archives, [S.l.], v. 12, n. 10, oct. 2024. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/5890>. Date accessed: 05 dec. 2024. doi: https://doi.org/10.18103/mra.v12i10.5890.
Section
Research Articles

References

1. European Medicines Agency Committee for Medicinal Products for Human use (CHMP) Formulations of choice for the paediatric population. Reference Number: EMEA/CHMP/PEG/194810/2005
2. Zajicek, A.; Fossler, M.J.; Barrett, J.S.; Worthington, J.H.; Ternik, R.; Charkoftaki, G.; Lum, S.; Breitkreutz, J.; Baltezor, M.; Macheras, P.; et al. A report from the pediatric formulations task force: Perspectives on the state of child-friendly oral dosage forms. AAPS J. 2013, 15, 1072–1081.
3. Thomas F. Avoiding Bitter Taste. Pharmaceutical Technology 11-02-2019, Volume 43, Issue 11 Pages: 26–29
4. Stone, H., & Sidel, J. L. (2004). Sensory Evaluation Practices. Academic Press Inc., Tragon Corporation.
5. Latha RS, Lakshmi PK. Electronic tongue: An analytical gustatory tool. J Adv Pharm Technol Res. 2012 Jan;3(1):3-8.
6. Wang Z, Li J, Hong X, Han X, Liu B, Li X, Zhang H, Gao J, Liu N, Gao X, Zheng A. Taste Masking Study Based on an Electronic Tongue: The Formulation Design of 3D Printed Levetiracetam Instant-Dissolving Tablets. Pharm Res. 2021 May;38(5):831-842.
7. Podrażka M, Bączyńska E, Kundys M, Jeleń PS, Witkowska Nery E. Electronic Tongue-A Tool for All Tastes? Biosensors (Basel). 2017 Dec 31;8(1):3. doi: 10.3390/bios8010003.
8. Woertz K, Tissen C, Kleinebudde P, Breitkreutz J, Taste Sensing Systems (Electronic Tongues) for Pharmaceutical Applications, International Journal of Pharmaceutics, Volume 417, Issues 1–2, 2011, Pages 256-271
9. Liu S, Zhu P, Tian Y, Chen Y, Liu Y, Wang M, Chen W, Du L, Wu C. A Taste Bud Organoid-Based Microelectrode Array Biosensor for Taste Sensing. Chemosensors. 2022; 10(6):208.
10. Chen P, Wang B, Cheng G, Wang P. Taste receptor cell-based biosensor for taste specific recognition based on temporal firing. Biosens Bioelectron. 2009 Sep 15;25(1):228-33.
11. Cocorocchio M, Ives R, Clapham D, Andrews PL, Williams RS. Bitter Tastant Responses in the Amoeba Dictyostelium Correlate with Rat and Human Taste Assays. ALTEX. 2016;33(3):225-36.
12. Soto J et. al Rats can predict aversiveness of Active Pharmaceutical Ingredients, European Journal of Pharmaceutics and Biopharmaceutics, Volume 133, 2018, Pages 77-84.
13. J. Bennett, A. Coburn, A. Coupe, D. Stedman, A. Taylor, A. Tyler, Development of a Zebrafish Model for Bitter Taste Assessment, International Journal of Pharmaceutics, Volume 536, Issue 2, 2018, Pages 521-522.
14. Lawless, H. T., & Heymann, H. (2010). Sensory evaluation of food: Principles and practices. Chapman & Hall.
15. M. O'Mahony, M. Goldenberg, J. Stedmon, J. Alford. Confusion in the use of the taste adjectives ‘sour’ and ‘bitter’ Chemical Senses, Volume 4, Issue 4, December 1979, Pages 301–318.
16. Vikas et. al. Taste Assessment Trials for Sensory Analysis of Oral Pharmaceutical Products Pak. J. Pharm. Sci., Vol.21, No.4, October 2008, pp.438-450.
17. Morris JB, Tisi DA, Tan DCT, Worthington JH. Development and Palatability Assessment of Norvir® (Ritonavir) 100 mg Powder for Pediatric Population. Int J Mol Sci. 2019 Apr 6;20(7):1718.
18. Strickley RG. Pediatric Oral Formulations: An Updated Review of Commercially Available Pediatric Oral Formulations Since 2007. J Pharm Sci. 2019
19. Keane, P. The Flavor Profile. ASTM Manual on Descriptive Analysis Testing for Sensory Evaluation; ASTM International: West Conshohocken, PA, USA, 1992; pp. 2–15
20. Hort J et. al (Ed.). Time-Dependent Measures of Perception in Sensory Evaluation. West Sussex, UK: Wiley Blackwell.
21. International Council for Harmonisation (ICH). 2016. Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6 (R2).
22. Green BG, Lim J, Osterhoff F, Blacher K, Nachtigal D. Taste Mixture Interactions: Suppression, Additivity, and the Predominance of Sweetness. Physiol Behav. 2010 Dec 2;101(5):731-7.
23. Russell S.J Keast, Paul A.S Breslin, An Overview of Binary Taste–Taste Interactions, Food Quality and Preference, Volume 14, Issue 2, 2003, Pages 111-124.
24. B. DeFer, Food ingredients—Sweetener Technical Overview and Allowable Daily Intake (Adapted), The NutraSweet Company, Chicago, 2010. 22.
25. Drašković, M., Medarević, D., Aleksić, I., & Parojčić, J. (2016). In Vitro And In Vivo Investigation of Taste-Masking Effectiveness of Eudragit E PO as Drug Particle Coating Agent in Orally Disintegrating Tablets. Drug Development and Industrial Pharmacy, 43(5), 723–731.
26. Szejtli, J., and L. Szente. Elimination Of Bitter, Disgusting Tastes of Drugs and Foods by Cyclodextrins European Journal of Pharmaceutics and Biopharmaceutics 61.3 (2005): 115-125.
27. Sriwongjanya M, Bodmeier R, Effect of Ion Exchange Resins on the Drug Release from Matrix Tablets, European Journal of Pharmaceutics and Biopharmaceutics, Volume 46, Issue 3, 1998, Pages 321-327.
28. Santagiuliana M, Broers L, et. al Strategies to Compensate for Undesired Gritty Sensations in Foods, Food Quality and Preference, Volume 81, 2020.
29. Imai, E., Hatae, K. And Shimada, A. (1995), Oral Perception of Grittiness: Effect of Particle Size and Concentration of The Dispersed Particles and The Dispersion Medium. Journal Of Texture Studies, 26: 561-576.