Assessing the homogeneity of Actimask® acetaminophen and N-acetyl glucosamine mixture to predict further steps in the development of orodispersible tablets

Keywords: N-acetyl-D-glucosamine, Acetaminophen, segregation, laser diffraction, orodispersible tablets, direct pressing, mixture uniformity, HPLC


One of the main problems in the production of tablets, which has significant negative consequences, is the segregation of the tablet mixture leading to inhomogeneity of dosage units, material losses in the manufacturing process and improperness of the specified pharmaceutical technical characteristics of the mixture.

The aim of the research. This work aims at the pharmaceutical technical study of the substances N-acetyl-D-glucosamine and Actimask® Acetaminophen and determination the uniformity of the powder mixture of active pharmaceutical ingredients (APIs) to predict the optimal technology for obtaining a pharmaceutical formulation with the acceptable properties.

Materials and methods. N-acetyl-D-glucosamine (Zhejiang Candorly Pharmaceutical, China) and Actimask® Acetaminophen (SpiPharma, USA) were used.

Scanning probe microscope Solver P47N-PRO ("NT-MDT", Russia), optical microscope, flowability tester VP-12A, laser diffraction particle size analyzer SALD-2201 ("Shimadzu", Japan), liquid chromatograph Agilent 1260 Infinity II with Diode Array Detector (Agilent Technologies, USA), spectrophotometers Shimadzu UV-1800 ("Shimadzu", Japan) were used.

The study of API pharmaceutical technical properties (microscopic characteristics, moisture absorption capacity, flowability, bulk volume and tapped volume, particle size distribution by sieve analysis and laser diffraction), as well as vibration simulation and following chromatographic study were carried out in this work.

Results and discussion. The shape of the particles N-acetyl-D-glucosamine and Actimask® Acetaminophen, which was determined by microscopic analysis, demonstrated the possibility of N-acetyl-D-glucosamine particles to stick to Actimask® Acetaminophen ones. The experimental study allowed to reveal the hygroscopicity of both APIs; poor flowability, unsatisfactory Hausner ratio, and Carr index for N-acetyl-D-glucosamine; excellent flowability, Hausner ratio, and Carr index for Actimask®. Vibration caused segregation of the powder mixture. It was found that all layers do not meet the requirements and an excessive content of Actimask® is registered, which indicates the stratification of the powder mixture.

Conclusions. The physical properties of the substances were determined and found to have significant differences in their particle size distribution. Segregation of the mixture after vibration was confirmed by laser diffraction and assay analysis. In order to solve the segregation problem, the granulation of N-acetyl-D-glucosamine may be proposed.


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Author Biographies

Ihor Zupanets, National University of Pharmacy

Department of Industrial Technology of Drugs

Оlena Ruban, National University of Pharmacy

Department of Industrial Technology of Drugs

Tetiana Kolisnyk, National University of Pharmacy

Department of Industrial Technology of Drugs

Yurij Stolper, State Scientific Institution "Institute for Single Crystals" of National Academy of Sciences of Ukraine

Laboratory of Technology and Analysis of Medicinal Products


Deutsche Gesellschaft für Allgemeinmedizin und Familienmedizin. (2018). Chronischer Schmerz (AWMF-Registernr. 053/036). Available at:

Singh, M. K. (2021). Chronic Pain Syndrome Medication. Medscape. Available at:

Chronic pain: supporting safer prescribing of analgesics (2017). British Medical Association. Available at:

Nikles, C. J., Yelland, M., Del Mar, C., Wilkinson, D. (2005). The Role of Paracetamol in Chronic Pain: An Evidence-Based Approach. American Journal of Therapeutics, 12 (1), 80–91. doi:

Rachin, A. P., Sharov, M. N., Averchenkova, А. А., Vygovskaya, S. N., Nuvakhova, M. B. (2017). Chronic pain: from pathogenesis to innovative treatment. RMJ, 9, 625–631. Available at:

Saleem, T. H., Abo El-Maali, N., Hassan, M. H., Mohamed, N. A., Mostafa, N. A. M., Abdel-Kahaar, E., Tammam, A. S. (2018). Comparative Protective Effects of N-Acetylcysteine, N-Acetyl Methionine, and N-Acetyl Glucosamine against Paracetamol and Phenacetin Therapeutic Doses–Induced Hepatotoxicity in Rats. International Journal of Hepatology, 2018, 1–8. doi:

Reducing Powder Segregation – a big issue especially in vacuum conveying systems. LFA Machines. Available at:

Understanding And Solving Segregation Effects In Pharmaceutical Solid-Dosage Form Operations. (2018). Pharmaceutical Online. Available at:,in%20an%20inconsistent%20final%20product

Particle Segregation Testing Instrument (2018). Pharmaceutical Online. Available at:

Delft Solids Solutions. (2016). Segregation of Powders (No. 2). Available at:

Shah, K. R., Farag Badawy, S. I., Szemraj, M. M., Gray, D. B., Hussain, M. A. (2007). Assessment of Segregation Potential of Powder Blends. Pharmaceutical Development and Technology, 12 (5), 457–462. doi:

Skibsted, E. T. S., Boelens, H. F. M., Westerhuis, J. A., Witte, D. T., Smilde, A. K. (2006). Simple assessment of homogeneity in pharmaceutical mixing processes using a near-infrared reflectance probe and control charts. Journal of Pharmaceutical and Biomedical Analysis, 41 (1), 26–35. doi:

Chung, Y.-C., Liao, C.-C., Zhuang, Z.-H. (2021). Experimental investigations for the effect of fine powders on size-induced segregation in binary granular mixtures. Powder Technology, 387, 270–276. doi:

Fan, Y., Hill, K. M. (2015). Shear-induced segregation of particles by material density. Physical Review E, 92 (2). doi:

Arntz, M. M. H. D., Beeftink, H. H., den Otter, W. K., Briels, W. J., Boom, R. M. (2013). Segregation of granular particles by mass, radius, and density in a horizontal rotating drum. AIChE Journal, 60 (1), 50–59. doi:

Liao, C.-C., Ou, S.-F., Chen, S.-L., Chen, Y.-R. (2020). Influences of fine powder on dynamic properties and density segregation in a rotating drum. Advanced Powder Technology, 31 (4), 1702–1707. doi:

Linek, J. (2007). Annual Report 2006. Institute of Chemical Process Fundamentals of the ASCR, V.V.I. Prague.

Jaklič, M., Kočevar, K., Srčič, S., Dreu, R. (2015). Particle size-based segregation of pharmaceutical powders in a vertical chute with a closed bottom: An experimental evaluation. Powder Technology, 278, 171–180. doi:

State Pharmacopoeia of Ukraine (SPU). Vol. 1 (2015). SE “Pharmacopoeia Centre.”

Commission Directive 2003/63/EC (2003). The Official Journal of the European Union, L159.

Zhong, Y., Bauer, B. A., Patel, S. (2011). Solvation properties of N-acetyl-β-glucosamine: Molecular dynamics study incorporating electrostatic polarization. Journal of Computational Chemistry, 32 (16), 3339–3353. doi:

Devriendt, L., Gatumel, C., Berthiaux, H. (2013). Experimental Evidence of Mixture Segregation by Particle Size Distribution. Particulate Science and Technology, 31 (6), 653–657. doi:

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How to Cite
Zupanets, I., RubanО., Kolisnyk, T., & Stolper, Y. (2021). Assessing the homogeneity of Actimask® acetaminophen and N-acetyl glucosamine mixture to predict further steps in the development of orodispersible tablets. EUREKA: Health Sciences, (5), 69-80.
Pharmacology, Toxicology and Pharmaceutical Science