Granulation with Dow Cellulosic Polymers II. High Shear Granulation

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METHOCEL E5P LV was there a statistically significant increase in hardness at the higher binder level. There was no statistically significant difference in the hardness for 3% and 6% levels of METHOCEL A15P LV. The HPC products did give slightly harder tablets relative to the METHOCEL products, with the exception of METHOCEL K3P LV as noted above. With hydroxypropylcellulose, hardness did increase with binder concentration. Povidone clearly produced quite hard tablets, especially the K90 viscosity grade; this polymer, as did the HPC, produced the more expected relationship between hardness and binder level. The friabilities were all < 0.5%, even for the softest of tablets. Even though some of the cellulosic binders produced tablets that were several SCU softer than the tablets produced using PVP, the friabilities were usually comparable. For example, note in Table 10 the values of hardness and friability for 6% METHOCEL K3P LV, 6% HPC-EF, and 6% PVP (K90). The span of tablet weight variation (n=20) was from 1.53% RSD (relative standard deviation, standard deviation/mean x 100) for PVP (K90) at 3% to 0.56% RSD for HPC-EF at the 6% use level. This range is slightly more than the range observed for the acetaminophen granulations, but slightly less than the range observed for the Vitamin C granulations. The RSD of tablet thickness variations was also quite uniform, ranging from 0.59% (3% E5P LV) to 0.23% (for both 3% METHOCEL A15P LV and PVP (K29-32). Table Dissolution Properties The in vitro dissolution curves for the methazolamide tablets were recorded under USP conditions (Type 2 apparatus, 100 rpm, 900 mL of pH 4.5 acetate buffer) and are given in Figures 41-46. The USP limits are 24 High Shear Granulation: Methazolamide Model
75% drug release in 45 minutes; the actual time that this amount of drug was liberated is denoted by t 75% . As was done in previous sections, the relative performance of the 5 METHOCEL products will be examined first. In Figure 41, it can be clearly seen that there is essentially no difference in the time for dissolution when the binders were used at 3% w/w; the tablets prepared with METHOCEL A15P LV were just slightly faster to dissolve. When the binder is increased to 6% w/w (Figure 42), there is virtually no shift in the dissolution behavior of tablets prepared with METHOCEL A15P LV. The tablets prepared with the METHOCEL E5P LV, E15P LV, and F4P LV required 6-8 minutes more time for dissolution with t 75% ≈ 25 minutes. The 6% level of METHOCEL K3P LV as binder caused the tablets to require 12 additional minutes compared to the 3% level, but this was still one-third less than the specified 45 minutes. In Figures 43 and 44, comparisons are shown between two METHOCEL products and the two HPC products. At 3% binder (Figure 43), HPC-EF and HPC-LF perform in a manner similar to the hypromellose materials shown in Figure 41. Considerably more variety is exhibited at the 6% level (Figure 44). The lower molecular weight hydroxypropylcellulose gave t 75% of 37 minutes, while HPC-LF gave t 75% of 51 minutes, or 6 minutes longer than the USP specification. Figures 45 and 46 compare the METHOCEL A and K products with the PVP polymers. At 3% binder (see Figure 45), the K90 grade of PVP shows a somewhat longer drug release, although still well within limits. At 6% binder, shown in Figure 46, the lower viscosity povidone has a dissolution profile that is nearly intermediate between that of the METHOCEL polymers, while the PVP (K90) material gave t 75% of 52 minutes. High Shear Granulation: Methazolamide Model 25
Page 1 and 2: Granulation with Dow Cellulosic Pol
Page 3 and 4: Properties of the Granulation The c
Page 5 and 6: High Shear Granulation: Acetaminoph
Page 7 and 8: Tablet Physical Properties The hard
Page 9 and 10: High Shear Granulation: Acetaminoph
Page 11 and 12: The remaining figures in this secti
Page 13 and 14: and substantially more material
Page 15 and 16: It was observed previously that the
Page 17 and 18: High Shear Granulation: Vitamin C M
Page 19 and 20: METHOCEL A and METHOCEL K products
Page 21 and 22: Model Formulation 3: Methazolamide
Page 23: products; the amount of fines was a
Page 28: For more information, complete lite

Granulation with Dow Cellulosic Polymers II. High Shear Granulation

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