Vibratory mixing of pharmaceutical powders on a single-tablet-scale
A single-tablet-scale mixing process, being part of a setup for the production of individualized tablets, is developed and studied. The process relies on the principle of vibratory mixing to achieve a homogeneous powder blend in the order of seconds. To investigate the mixing performance under various frequencies and amplitudes, a contactless evaluation method was implemented based on high-speed video recordings, a colored tracer and image analysis.
The high spatial and temporal resolution of the recordings proved a valuable tool to assess the quality of the mixing process. Depending on the vibration parameters, different intensities of diffusive and convective mixing were observed. It was found that for similar accelerations, lower frequencies lead to faster mixing. Applying vibrational frequencies of 100 and 150 Hz and accelerations of 112 g a homogeneous blend of Emcocel 90 M and dyed Avicel PH-102 was produced within 2 s. This indicates the suitability of this approach for the use in the design of a small-scale direct compression process.
Materials: Two pharmaceutical powder materials were used. As the aim was to develop a technique to assess mixing quality on a visual basis no APIs were used. This was done as a first step in order to demonstrate proof-of-concept without the safety concerns of working with APIs. The focus was on pharmaceutical relevance and the suitability for dyeing the powders with a water-soluble coloring agent. Therefore, we chose two microcrystalline celluloses (MCC), i.e., Emcocel 90 M (E-90) and Avicel PH-102 (A-102) having a nominal mean particle size of 90 μm and 100 μm respectively . Both powders are widely used as fillers and binding agents in direct compression formulations. They show good disintegration behavior and lead to high tensile strength in tablets even at low compaction pressures [13,50].
The optical difference between the two materials was achieved by using as-received Emcocel 90 M (JRS Pharma LP, Rosenberg, Germany) and Avicel PH-102 (FMC Biopolymer, Philadelphia, United States) dyed with red food color (No-taste Red Icing Color, Wilton Industries, USA), see Fig. 3. The optical microscope images in Fig. 3 show a higher content of needle-shaped particles in Emcocel than in the dyed Avicel, which is also reflected in their flowability.
Article information: Andreas Kottlan, Benjamin J. Glasser, Johannes G. Khinast. Vibratory mixing of pharmaceutical powders on a single-tablet-scale, Powder Technology, Volume 387, 2021. https://doi.org/10.1016/j.powtec.2021.04.040.