Real-Time Particle Size Analysis Using Focused Beam Reflectance Measurement as a Process Analytical Technology Tool for a Continuous Granulation–Drying–Milling Process

Abstract

Focused beam reflectance measurement (FBRM) was used as a process analytical technology tool to perform inline real-time particle size analysis of a proprietary granulation manufactured using a continuous twin-screw granulation-drying-milling process. A significant relationship between D20, D50, and D80 length-weighted chord length and sieve particle size was observed with a p value of <0.0001 and R(2) of 0.886. A central composite response surface statistical design was used to evaluate the effect of granulator screw speed and Comil® impeller speed on the length-weighted chord length distribution (CLD) and particle size distribution (PSD) determined by FBRM and nested sieve analysis, respectively. The effect of granulator speed and mill speed on bulk density, tapped density, Compressibility Index, and Flowability Index were also investigated. An inline FBRM probe placed below the Comil-generated chord lengths and CLD data at designated times. The collection of the milled samples for sieve analysis and PSD evaluation were coordinated with the timing of the FBRM determinations. Both FBRM and sieve analysis resulted in similar bimodal distributions for all ten manufactured batches studied. Within the experimental space studied, the granulator screw speed (650-850 rpm) and Comil® impeller speed (1,000-2,000 rpm) did not have a significant effect on CLD, PSD, bulk density, tapped density, Compressibility Index, and Flowability Index (p value > 0.05).

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“…The D10, D50, and D90 chord length (CL) values were calculated with the icFBRM 4.2 software from a cumulative percent distribution, which was produced from the CLD. The cumulated percent of CL size that accounts for 50 % or less of the CL (which is the 50th percentile) is called D50 . The same procedure was used to determine D10 and D90.…”

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“…Only a small range of moisture contents was evaluated (0.43-1.06% w/w, measured with KF). After the fluid-bed granulator, a continuous mill was installed and the particle-size distribution of milled granules was evaluated by focused beam reflectance measurement (FBRM) [35].…”