(W1130-08-49) In Line Particle Size Detection in Roll Compaction

Purpose: Roll compaction as a form of dry granulation is a commonly used granulation technique to improve flowability, content uniformity and density prior to tablet compression. One of the main factors that determines flowability is particle size distribution. Small particles, or fines, can hinder bulk powder flowability due to their small size, high packing factor, and irregular shapes. Having reliable particle size data to determine the effectiveness of a granulation is key in predicting how the powder will perform on a high speed tablet press. There are several methods used to determine particle size offline, with a ro-tap and sieve stacks being a commonly used one to determine size fractions at different size cutoffs, to imaging methods including shadow capture, laser diffraction, or light scattering. All of these methods in the offline form take time to perform, which could result in a large amount of material being wasted while the samples are processing. Using the Parsum IPP-80 probe (Malvern Panalytical), particle size was able to be read instantaneously on granules coming off of a roll compactor, the TFC-220® (Freund-Vector Corporation). This study aimed to prove that particle sizes could be measured accurately in line with roll compaction when compared to offline measurements and determining the resulting physical characteristics such as flowability and density.

Methods: Roll compaction dry granulation was done using the roll compactor with flat, serrated rolls, milled with a 2.0mm punched hole mill screen, and the resulting particles were measured by three different analytical methods: In line with the Parsum IPP-80 probe (Malvern Panalytical), offline with the QICPIC particle size analyzer (Sympatec), and a sieve stack consisting of 10, 18, 30, 40, 70, and 270 mesh screens using the Ro-tap to separate the fractions. A placebo formulation of 70% lactose monohydrate (Granulac 200), 29.5% microcrystalline cellulose (Emcocel 50M) and 0.5% magnesium stearate. Compaction of the raw material was done at the following process parameters: Force = 7500lbf, roll speed = 5rpm, screw speed = 15rpm, mill speed = 50rpm and deaeration vacuum on. Product fell through the Parsum IPP-80 probe and was collected in a stainless-steel vessel for offline measurements in the Ro-tap and QICPIC. Hausner ratio and Carr’s index were used to determine flowability characteristics of the granulated material.

Results: The particle size distribution (D10, D50, and D90) of the raw and roll compacted material are shown (in microns) in the two tables below: There are limitations to each device used to determine particle sizes, which lends itself to variability between measurement methods. However, there is a clear difference between the raw material and granulated material in terms of particle size, and that trend is captured by all three devices clearly showing significant particle size growth from the raw material to the final product. The raw material had a Hausner ratio = 1.43 and corresponding Carr’s index of 30.03, where a Hausner ratio >1.34 indicates poor flowability. Conversely, the granulated powder had a Hausner ratio of 1.28 and Carr’s index of 22.0, indicating significant improvement in flowability.

Conclusion: Using inline particle size analysis allows for increased response time to process upsets that can reduce out of specification material, as well as indicating the influence that changing process parameters will have on the resulting particles. It can also reduce the amount of sampling needing to be done by operators since it captures material as it’s falling from the mill into the collection medium. If deviations occur in downstream processing, engineers have another data point to reflect on during root cause analysis of the failure, which can drastically reduce investigation times as well.

Raw Material PSD

Roll Compacted Material PSD