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6 MEGGLE | Co-processed lactose CombiLac ® Compactibility Co-processed CombiLac ® vs. MicroceLac ® 100 and StarLac ® Tablet hardness (N) 250 0 0 20 Compaction force (kN) Tablet press: IMA Styl´one 105ML, Tablets: Ø 11.3 mm, 500 mg CombiLac ® MicroceLac ® 100 StarLac ® Compactibility Co-processed CombiLac ® vs. physical admixture Tablet hardness (N) 250 0 0 20 Compaction force (kN) Tablet press: IMA Styl´one 105ML, Tablets: Ø 11.3 mm, 500 mg CombiLac ® Physical admixture Figure 6: Volume flow rate (ml/s) as a function of aperture size (mm) for CombiLac ® analyzed by a FlowRatex ® . Flowability Index (FI) of MEGGLE's triple co-processed excipient CombiLac ® , is 2 (mm). Compactibility Material fill characteristics and compression behavior of formula- tion ingredients impact tablet quality. Generally, compaction performance is enhanced by combination of brittle and plastically deforming materials. However, addition of elastically deforming components, e. g. various starches, seems to be diametrically opposed. Pharmaceutical practice is often positioned to balance the integrity of a solid dosage form and its function as a pharma- cological vehicle. CombiLac ® is well-balanced by insuring sufficient tablet hardness and, simultaneously, fast disintegration time. Additionally, CombiLac ® offers superior hardness yield in compar- ison to the physical admixture of individual ingredients. An increase of approximately 20 % is achieved (Figure 8). Tablet hardness profiles of co-processed excipients MicroceLac ® 100 (75 % alpha-lactose monohydrate and 25 % MCC) and StarLac ® (85 % alpha-lactose, and 15 % native corn starch) are provided for reference (Figure 9). Figure 7: Typical powder functional values for triple co-processed excipient CombiLac ® . All methods were performed according to compendial standards. BET surface area determination was conducted by an instru- mented Quantachrome Autosorb iQ (Adsorbent K 2 , outgas time and temperature: 7 hrs at 50 °C, in vacuo). Figure 8: Tablet hardness profile for CombiLac ® compared to a physical admixture of individual components (spray-dried lactose grade FlowLac ® 100, MCC 102, and pregelatinized DC starch grade Starch ® 1500). Tablets were produced using a tablet press IMA Styl'One 105 ML, with a tablet diameter of 11.3 mm, a weight of 500 mg, and 0.5 % Mg-stearate. Figure 9: Tablet hardness profile for CombiLac ® compared to co-processed excipients MicroceLac ® 100 (75 % alpha-lactose monohydrate and 25 % MCC), and StarLac ® (85 % alpha-lactose monohydrate and 15 % native corn starch) are depicted for reference. Tablets were produced using a tablet press IMA Styl'One 105 ML, with a tablet diameter of 11.3 mm, a weight of 500 mg, and 0.5 % Mg-stearate. 10 10 5 5 15 15 Volume flow Co-processed CombiLac ® Volume flow rate (ml/s) 8 0 0 9 Aperture (mm) CombiLac ® 7 6 5 4 3 2 1 200 200 150 150 100 100 50 50 Flowability Co-processed lactose Angle of repose (°) Density bulk (g/l) Density tapped (g/l) Hausner ratio Carr's index (%) BET-surface (m 2 /g) CombiLac ® 30 450 540 1.19 16 0.49 1 3 5 7 2 4 6 8 Functional related characteristics Powder flow Flow assessments are routinely completed in solid dosage form development and strongly impact production and product quality. Amongst the various methods used to evaluate powder flow, a FlowRatex ® apparatus (Powder flow through an aperture) is widely used. CombiLac ® shows good flowability, reflected by a low Flowability Index, FI = 2 (mm), and high volume flow rates as shown in figure 6. Also, compressibility related indices and angle of repose are common and had been used for comparison (Figure 7). Specific surface If the physical admixture comprising 70 % alpha-lactose mono- hydrate, 20 % MCC and 10 % white, native corn starch is com- pared to the triple co-processed excipient CombiLac ® , only a marginal impact on BET surface area is observed. The overall BET surface area is measured to be 0.5 m 2 /g.