High precision mid-range particle size reduction using an impact conical mill

1. High precision mid-range particle size reduction using an impact conical mill X. Kou, E. L. L. Cheah, L. W. Chan, P. W. S. Heng GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, National University of Singapore Table 1. Experimental conditions studied Introduction Group Impeller speed (rpm) Blower speed (rpm) Screen size (inch) d50 (µm) Span 1 5500 3600 83 46.7 3.9 2 5500 3600 45 32.8 3.8 3 5500 5000 83 63.9 3.5 4 4000 3600 62 37.4 2.9 5 7000 4300 45 28.9 3.2 6 5500 4300 62 22.7 3.2 7 4000 5000 62 49.7 4.0 8 5500 4300 62 21.1 3.2 9 7000 4300 83 39.0 3.1 10 4000 4300 83 47.6 3.9 11 7000 5000 62 41.8 2.7 12 4000 4300 45 38.7 3.7 13 7000 3600 62 20.6 3.1 14 5500 5000 45 42.2 3.3 15 5500 4300 62 22.5 3.1 Particle size reduction is a very important unit operation in the pharmaceutical industry. Production of mid-range particles of narrow size distribution remains a challenge. The aim of this study was to investigate the efficiency of a newly developed impact conical mill at comminuting coarse drug particles to produce particles of narrow size distribution and in the mid-size range (20 – 100 µm). Methods The Box-Behnken design was used to identify the influence of factors affecting the sizereduction process using the impact conical mill (Fine Grind F10, Quadro Engineering, Canada). Three process variables, namely impeller speed, blower rate and screen aperture size, were studied. The blower rate refers to the air flow rate controlling the conveyance of material from the milling chamber to the product collector. In each run, 300 g of coarse acetaminophen crystals(Granules, India) were fed directly into the milling chamber. The d10, d50 and d90 values (representing the 10th, 50th and 90th percentiles of the cumulative size plot respectively) of the coarse and milled acetaminophen powders were determined by laser diffractometry (LS 230, Coulter, USA) with a small volume module. The spread of the size distribution was represented by the span [(d90–d10)/d50], where a larger span value indicates a broader size distribution. Analysis of variance (ANOVA) was used to identify the significant factors affecting the size reduction process. Results & Discussion Fig.3. Effects of impeller speed and blower speed on span Fig.2. Effects of impeller speed and blower speed on particle size Particles of mid-size range were successfully produced using the impact conical mill. The coarse acetaminophen crystals (d50, 1095 µm; span, 0.85) were comminuted to produce particles with d50 in the targeted range of 20 to 70 µm. It was found that increased impeller speed resulted in smaller particles, while the opposite was observed when the blower speed or screen aperture size was increased. An increase in blower speed resulted in shorter residence time of the material in the milling chamber, hence reducing exposure to impact-attrition forces in the mill. On the other hand, an increase in screen aperture size allowed larger particles to pass through. While larger particle size was obtained, the accompanying size distribution was also wider. Conclusion Particles of narrow size distribution in mid-size range were successfully produced by the impact conical mill. This mill shows great potential for targeted size reduction of drug powders.Of the variables studied, the screen aperture size was the major factor affecting the particle size distribution while the impeller speed had the greatest influence on the degree of size reduction. Fig. 1. Experimental set-up