Issue link: https://www.e-digitaleditions.com/i/1331851
40 January/February 2021 Tablets & Capsules The disintegration time of six tab- lets was measured using an Erweka ZT122 disintegration tester. Results Figure 1 shows the PCA results for anhydrous lactose from both calculated from the tablet crushing strength (TCS), diameter (D) and tablet height (H) for FFBE tablets using the following formula: TTS = 2∙TCS [19] π∙D∙H air-jet-sieving particle size param- eters (%w/w <45 µm, %w/w <150 µm, %w/w <250 µm, and %w/w <355 µm). From each roller dryer, six edge-of-knowledge-space batches covering the historical variation were selected for further analysis. The particle size was measured using a Sympatec Helos dry pow- der laser diffraction analyzer with an R5 lens. Samples were measured on a 100-millisecond time base with a feed rate of 50 percent and a pressure of 0.5 bar. Differential scanning calorimetry (DSC) was performed using a Mettler Toledo DSC instrument. Ten milligrams of material were weighed into a 40 microliter standard aluminum pan and crimped with an aluminum pierced lid. Analyses were con- ducted from 20° to 250°C at a heat- ing rate of 10°C/min. F i v e - h u n d r e d - g r a m f o r m u l a - tions were prepared by blending 95.5 percent w/w anhydrous lactose with 4 percent w/w croscarmellose sodium (Primellose, DFE Pharma) for 8 minutes at 90 rpm in a Turbula blender. Prior to blending, both ingredients were stored overnight in a Heraeus climate chamber at 20°C and 30 percent relative humidity. After initial mixing, 0.5 percent w/w magnesium stearate (Sigma Aldrich) was added, and the blend was mixed again for 2 minutes at 90 rpm. Tablets were compressed using a Luxner RoTab T rotary press operating at 25 rpm with a dwell time of 60 milliseconds. The die filling depth was set to obtain 250-milligram tablets. Tablets were compressed at 10 and 15 kilonew- tons using flat-face, beveled-edge (FFBE) punches (I Holland) with a diameter of 9 millimeters. Twenty tablets were analyzed for tablet crushing strength, weight, d i a m e t e r , a n d t h i c k n e s s u s i n g an automated tablet tester (Sotax HT100). The tablet breaking force was measured at a constant speed of 2 mm/s, and the maximum force needed to break the tablets was used as the tablet crushing strength. The tablet tensile strength (TTS) was Figure 1 Principal component analysis score plot for more than 150 batches of SuperTab 21AN, taken over 4 years from roller dryer 1 (RD1) and roller dryer 2 (RD2) (All data points are well within specification.) t[2] 5 4 3 2 1 0 -1 -2 -3 -4 t[1] -5 -4 -3 -2 -1 0 1 2 3 4 R2x[1] = 0.171 R2x[2] = 0.145 RD1—2017 RD1—2018 RD1—2019 RD1—2020 RD2—2020 Hotelling's T2 95% confidence limit Figure 2 Principal component analysis score plot for more than 150 batches of SuperTab 21AN (All batches are well within specification. Clustering of colors indicates a small trend in the data comparing before and after laboratory move.) t[2] 5 4 3 2 1 0 -1 -2 -3 -4 t[1] -5 -4 -3 -2 -1 0 1 2 3 4 R2x[1] = 0.171 R2x[2] = 0.145 Hotelling's T2 95% confidence limit RD1—2017 RD1—2018 RD1—2019 RD1—2020 (Q1) RD1—2020 (Q2-4) RD2—2020 (Q1) RD2—2020 (Q2-4)