Granulation with Dow Cellulosic Polymers II. High Shear Granulation

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Tablet Dissolution Properties Just as was the case with the in vitro dissolution curves for acetaminophen shown earlier, the release profiles varied both as a function of the type and amount of binder in the formulation. A USP Type 2 apparatus at 50 rpm and 900 mL of pH 7.0 phosphate buffer were used. A number of these dissolutions are given in Figures 28-34. There is no "USP specification" for Vitamin C tablets, but in order to facilitate comparisons with the acetaminophen data, limits of 80% released in 30 minutes have been added. The time to reach 80% dissolved is designated by t 80% . The five METHOCEL products evaluated in this study are compared in Figures 28-31. In Figure 28, dissolution behavior for a binder level of 3% using the solution binder addition method is shown. Here, the METHOCEL K3P LV gave the fastest dissolution (t 80% of 12.4 min), followed closely by the E5P LV and F4P LV grades at about 14 min. The METHOCEL E15P LV, by comparison, had t 80% of 19.4 min, clearly showing the effect of molecular weight/viscosity of hypromellose 2910 in this formulation. The methylcellulose product, METHOCEL A15P LV, produced the tablets that had the longest dissolution time, about 8 minutes longer than that of METHOCEL E15P LV. If one compares Figure 28 with Figure 29 (which illustrates the same binders at the same level, except that the dry binder addition method was used), it is clear that binder addition method is insignificant in this aspect of the binder performance as well. The rank order of the binders remains the same, with the t 80% times just slightly longer for the dry method. Note that the order present here is the same as that observed for Vitamin C in the fluid bed granulation study (Part I), but once again shows a reversal of the relative performance of the 18 High Shear Granulation: Vitamin C Model
METHOCEL A and METHOCEL K products compared to the acetaminophen model in both this study and the earlier fluid bed study. At the 6% binder level (Figures 30- 31), the order of tablet dissolution is the same as at 3% binder. The METHOCEL K3P LV, E5P LV, and F4P LV all gave very similar dissolution profiles (t 80% ≈ 21 min) when the solution addition method was used, followed by METHOCEL E15P LV about 10 minutes later. The METHOCEL A15P LV gave an almost sustained-release dissolution, with t 80% not reached until 82 minutes. Turning to the dry addition method (Figure 31), the order and general performance of the binders was not different from that in the solution method. There was a slightly larger spread in the dissolution behavior of the K3P LV, E5P LV, and F4P LV products, and the A15P LV tablets achieved 80% release in about 72 minutes. As has been consistently observed throughout these granulation studies, increasing the amount of binder gives longer tablet dissolution times and accentuates differences in the relative performance of the binders. The remaining figures in this section compare the dissolution behavior of METHOCEL K3P LV (which was essentially equivalent to that of the METHOCEL E5P LV and F4P LV products in this formulation) with the HPC products and the other competitive binders. In Figure 32, it is seen that there is practically no difference in the dissolution profiles for METHOCEL K3P LV, HPC-EF, and HPC-LF, regardless of the binder addition method, at the 3% binder level. At the 6% level (not shown), the two HPC products had almost identical dissolution profiles, again irrespective of the way in which the binder was placed in the granulations; the t 80% values were 27-29.5 minutes vs. 19 minutes for the METHOCEL K3P LV. High Shear Granulation: Vitamin C Model 19
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: High Shear Granulation: Vitamin C M
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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