Issue link: https://www.e-digitaleditions.com/i/1173734
36 October 2019 Tablets & Capsules The particle size, bulk and tapped density, and spe- cific surface area values for these batches are shown in Table 1. The particle size data for the eight selected batches indicates a high consistency for the product manufactured during the years studied. This is in align- ment with the R 2 (x) values of PC 1 and PC 2 indicating that only 29.8 percent of the variation can be explained by the data (Figure 2). The particle size data are in agreement with Hagrasy, et al. [14], and Moolchandani, et al. [15], which reported x50 values between 142 and 149 microns and an x90 value of 287 microns for this product. The bulk and tapped density range shows little variation, and the tapped densities are consistent with the literature [15]. The calculated Hausner ratios from the tested batches range between 1.20 and 1.25, indicating a fairly flowable powder. The specific surface area results did not show any significant differences between the batches tested. The thermal data for the eight knowledge-space batches are shown in Table 2. These results are consistent with literature values, as the DSC traces did not show an exothermic event around 167° to 174°C associated with amorphous lactose [16, 17]. The DSC data show an endothermic transition event associated with the dehy- dration of the incorporated crystalline water between 140° and 145°C for all samples [18], with subsequent melting of the alpha-anhydrous form (between 200° and 220°C) and decomposition of lactose [19]. The TGA shows a weight loss by dehydration of 4.5 to 4.6 percent, which is in alignment with literature values [16]. Compaction and disintegration The six knowledge-space batches that were near or outside the Hotelling's T 2 95 percent confidence interval recorded in seconds, and the average disintegration time was used. Results and discussion The PCA score plot is shown in Figure 2. As the fig- ure shows, the R 2 (x) of the first two components was 0.298, meaning that there was little trend in the data, as 29.8 percent of the variation is explained by PC 1 and PC 2. The overlap between colors representing the different production years indicates that there was a high degree of similarity between batches from the years tested. Additionally, no clusters or shifts in the year-to-year data were observed. Figure 3 shows the loading plot of the same data- set. The figure shows that the highlighted densities and particle-size parameters are the key contributors to the variation depicted in Figure 2. Other parameters, such as the specific rotation, moisture (by Karl Fischer titration), and the acidity of the lactose, did not vary significantly within the production data set. Selection of batches for further evaluation Specific batches were selected from the dataset to perform functional testing, as shown in Figure 4. To understand the variation observed, six batches were selected near or outside the Hotelling's T 2 95 percent confidence limit (represented by the blue ellipse in the figure). These batches are well suited for understanding the maximum variability delivered to users/customers and should be representative of the largest batch-to- batch variability. Two batches were taken from the mid- point of the spread in data (or knowledge space). Samples of these eight batches were taken from retained storage and further analyzed. Table 1 Additional physical parameters tested on eight knowledge-space batches of SuperTab 30GR Product batch Particle size* (microns) Density** (kg/m 3 ) Specific surface area** (m 2 /g) x10 x50 x90 Bulk Tapped 1 30.4±0.4 132±2 298±5 565 667 0.33 2 32.0±1.0 143±5 312±7 561 681 0.30 3 32.1±0.6 132±3 294±15 540 660 0.32 4 36.3±0.7 140±4 306±16 541 676 0.28 5 34.1±0.6 135±5 321±9 549 659 0.30 6 33.0±0.7 129±3 288±16 548 665 0.29 7 32.4±0.5 140±4 331±11 580 710 0.29 8 31.9±0.6 142±5 322±12 584 715 0.31 * measured five times (±x.x is 2 times the standard deviation) ** measured in duplicate