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