Granulation with Dow Cellulosic Polymers II. High Shear Granulation

More documents

Recommendations

Info

Tablet Physical Properties The hardness and friability of the 0.5 inch tablets compressed at 2000 lbs. total compression force are given in Table 7 for the wet binder addition method, and in Table 8 for the dry addition method. For all measurements, 20 tablets were used; the reported friabilities are those after 4 minutes in a Roche-type friabilator. The hardness and friability data can be analyzed in a number of ways. For the most part, tablets of satisfactory hardness and friability were obtained with each of the binders. From an inspection of Table 7, the top 5 binders in terms of hardness are 6% HPC-LF, 6% METHOCEL E15P LV/6% PVP (K90), 3% PVP (K90), and 6% HPC-EF. Similarly, the Table 7 BINDERS IN SOLUTION Hardness Friability (SCU) ± sd (%) 3% A15P LV 11.9 ± 0.7 0.42 6% A15P LV 9.8 ± 0.9 0.45 3% E5P LV 9.5 ± 0.9 0.63 6% E5P LV 10.2 ± 1.0 0.53 3% E15P LV 9.2 ± 1.0 0.54 6% E15P LV 13.0 ± 1.6 0.41 3% F4P LV 10.4 ± 0.7 0.58 6% F4P LV 11.2 ± 0.9 0.45 3% K3P LV 10.2 ± 1.0 0.66 6% K3P LV 10.7 ± 1.2 0.48 3% HPC-EF 9.8 ± 0.9 0.71 6% HPC-EF 12.1 ± 1.3 0.45 3% HPC-LF 10.2 ± 1.0 0.71 6% HPC-LF 13.4 ± 1.2 0.41 3% PVP (K29-32) 8.0 ± 1.5 1.06 6% PVP (K29-32) 11.5 ± 1.9 0.91 3% PVP (K90) 12.6 ± 1.6 0.56 6% PVP (K90) 13.0 ± 1.9 0.53 6% Acacia 6.0 ± 1.2 2.50 10% Pregel. Starch 11.1 ± 1.5 0.59 14 High Shear Granulation: Vitamin C Model best binders in terms of friability are 6% METHOCEL E15P LV/6% HPC- LF, 3% METHOCEL A15P LV, and 6% METHOCEL A15P LV, 6% METHOCEL F4P LV/6% HPC-EF. A similar inspection of Table 8 (dry binder addition method) shows that the top 5 binders in terms of hardness are 6% PVP (K90), 6% HPC-EF, 6% HPC-LF, and 6% METHOCEL E5P LV/3% PVP (K90). The least friable tablets in the "dry" case are 6% A15P LV, 6% HPC-LF, 6% HPC-EF, 3% METHOCEL E15P LV, and 6% METHOCEL E15P LV. Comparing the two sets of rankings for both hardness and friability, it is clear that the HPC products and PVP (K90) consistently gave the hardest tablets, while the HPC products, METHOCEL E15P LV, and Table 8 BINDERS DRY METHOCEL A15P LV were the binders that most consistently gave the lowest friabilities. If Tables 7 and 8 are examined for the 3 binders that gave the lowest values for hardness and the highest values for friability, it can be seen that PVP (K29-32) falls into both categories for both binder addition methods. The worst binder in those granulations prepared from binder solutions was acacia, with the 3% METHOCEL E15P LV tablets also being relatively soft. For the dry binder addition method, the 6% METHOCEL E15P LV tablets, along with the PVP (K29-32) tablets, among the softest. It is once again observed that there is not a simple inverse relationship between hardness and friability. Hardness Friability (SCU) ± sd (%) 3% A15P LV 10.3 ± 1.0 0.53 6% A15P LV 11.1 ± 0.7 0.41 3% E5P LV 10.1 ± 0.9 0.57 6% E5P LV 11.7 ± 1.3 0.54 3% E15P LV 9.5 ± 0.7 0.48 6% E15P LV 8.6 ± 0.7 0.49 3% F4P LV 11.0 ± 1.3 0.55 6% F4P LV 10.5 ± 1.0 0.56 3% K3P LV 9.6 ± 1.0 0.68 6% K3P LV 11.1 ± 1.3 0.54 3% HPC-EF 9.7 ± 1.0 0.67 6% HPC-EF 13.1 ± 1.4 0.45 3% HPC-LF 10.7 ± 1.0 0.72 6% HPC-LF 12.4 ± 1.2 0.44 3% PVP (K29-32) 7.2 ± 0.9 0.85 6% PVP (K29-32) 8.6 ± 0.9 0.79 3% PVP (K90) 11.7 ± 1.3 0.61 6% PVP (K90) 13.8 ± 1.9 0.49
It was observed previously that the hardest and least friable tablets were those which used 6% binder (with the exception of the 3% PVP (K90) tablets). Of the 18 sets of binders and binder addition methods in which the level was examined at both 3% and 6%, 13 sets showed statistically significant increases in hardness, 2 sets showed statistically significant decreases in hardness (METHOCEL A15P LV (solution) and METHOCEL E15P LV (dry), and 3 sets showed no statistically significant change (METHOCEL K3P LV and PVP (K90) in solution, and METHOCEL F4P LV in the dry state) with an increase in binder level. The significance of the binder addition method also may be examined. At the 3% binder level, only METHOCEL A15P LV, where the solution method gave harder tablets, and HPC-LF, where the dry method gave harder tablets, were statistically different. The METHOCEL E5P LV binder was "borderline" for p > 0.05. The remaining 6 binders did not exhibit a statistically significant difference in hardness due to the binder addition method. A much different case exists for the 6% binder level. Here, tablet hardnesses were different between the methods for 7 of the 9 binders. Granulations prepared when the binder was prehydrated gave harder tablets for METHOCEL E15P LV, METHOCEL F4P LV, HPC-LF, and PVP (K29-32). On the other hand, granulations prepared where the dry binder was added to the drug/lactose mix gave harder tablets for METHOCEL A15P LV, METHOCEL E5P LV, and HPC- EF. There was no statistically significant difference in hardness with binder addition methods for METHOCEL K3P LV and PVP (K90) at the 6% level. The differences in friability as a function of binder addition method were very minor. High Shear Granulation: Vitamin C Model 15
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 substantially more material
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

Create successful ePaper yourself

Delete template?

Save as template?