Granulation with Dow Cellulosic Polymers II. High Shear Granulation

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The METHOCEL products are compared in Figures 10-13. Figure 10 (solution binder addition method, 3% level) shows that the polymers all have t 80% of about 20 minutes with the exception of METHOCEL E15P LV, which had a t 80% of approximately 7 minutes longer, but which still passed the USP criteria. The dry binder addition method (Figure 11) shows more differentiation. METHOCEL E5P LV clearly was the fastest with a dissolution time of 15 minutes; METHOCEL A15P LV and F4P LV were next, with about the same time as was observed with the solution addition method. METHOCEL E15P LV was just 2-3 minutes slower than the solution method, with a t 80% right at the USP limit. (The dissolution results for the METHOCEL K3P LV product were anomolous and are not included pending repetition of the granulation.) Increasing the binder content to 6% resulted in the typical lengthening of the time for dissolution. In Figure 12, the curve for METHOCEL A15P LV is virtually unchanged from the 3% solution case. However, the remaining METHOCEL products are shifted to longer times, with METHOCEL F4P LV, E5P LV, and E15P LV all at t 80% ≈ 35 minutes, and with METHOCEL K3P LV at nearly 45 minutes. In the dry binder addition case (Figure 13), slightly different profiles were obtained. METHOCEL A15P LV, E5P LV, and F4P LV form one group with t 80% ≈ 25 minutes, while METHOCEL E15P LV and K3P LV both have t 80% greater than the USP limit, but with different curve shapes. 10 High Shear Granulation: Acetaminophen Model
The remaining figures in this section are comparisons of METHOCEL polymers with the HPC polymers, with the PVP products, and with acacia and pregelatinized starch. Figure 14 illustrates that using the dry addition method at 3% results in virtually no difference between the two viscosity grades of HPC, both having 80% drug dissolution in 25 minutes. If the same binders at the same level utilized the "solution" method, the HPC-LF gave the same release profile, while the HPC-EF gave a slightly longer (t 80% of 31 minutes) profile. Turning to the 6% level, Figure 15 shows the results of the solution method, with the HPC-EF and HPC-LF curves indistinguishable and with the time for 80% release at the USP limit. Using the dry addition method was not different in terms of the release profile for HPC-LF, but once again the EF grade had a slightly longer release with t 80% ≈ 32 minutes. Figures 16 and 17 compare two METHOCEL products with polyvinylpyrrolidone. The dry method at 3% (Fig. 16) shows that METHOCEL E5P LV and PVP (K29-32) are equivalent in dissolution behavior, with the K90 grade just slightly longer but well within the specified time period. The solution addition method gave results essentially the same. Turning to the 6% level (Fig. 17), METHOCEL A15P LV and PVP (K29-32) are practically equivalent, with the K90 polymer again slightly longer, now just within the specification. Using the dry method at the 6% binder level produced dissolution curves where the METHOCEL A15P LV was just slightly longer than the PVP (K90) and which was at the 30 minute limit. Lastly, a comparison of acacia, a pregelatinized starch, and METHOCEL A15P LV is illustrated in Figure 18. Here it appears that the derivatized starch is also acting as a disintegrant, giving the fastest drug release of all the binders evaluated. Acacia, despite giving quite soft and very friable tablets, nevertheless gave a somewhat unexpectedly long time for drug dissolution. Conclusions: Acetaminophen Model Formulation Granulations with acceptable densities and particle size distributions were obtained when 2 acetaminophen formulations having 3% and 6% binder levels were prepared in a high shear mixergranulator. There were only minor differences in these properties between granulations prepared by adding the binder as an aqueous solution or by adding the binder in a dry state to the active followed by granulation with water. The cellulosic polymers (METHOCEL and HPC products) tended to give granulations with a higher proportion of granules of 20-60 mesh, whereas the PVP binders produced somewhat more material in the 80-140 mesh region. With the given milling conditions, about 10% fines (
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: High Shear Granulation: Acetaminoph
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 and 24: products; the amount of fines was a
Page 25 and 26: 75% drug release in 45 minutes; the
Page 28: For more information, complete lite

Granulation with Dow Cellulosic Polymers II. High Shear Granulation

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