The Effect of Mill Type on Two Dry-Granulated Placebo Formulations - Pharmaceutical Technology

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The Effect of Mill Type on Two Dry-Granulated Placebo Formulations
The authors evaluate the effect of various mill types on particle-size distribution, flowability, tabletability, and compactibility.


Pharmaceutical Technology
Volume 32, Issue 11, pp. 72-86


Table VI: Microcrystalline cellulose–dibasic calcium phosphate compression properties.
Tableting. MCC–DCP formulation. Tablets were compressed and characterized for weight, thickness, and hardness. The mean weight values and corresponding relative standard deviations (RSDs) are listed in Table VI. Weight variation was below the desired RSD of 2.0% for all the conventional mill types. The two Gran-U-Lizer runs had slightly higher RSDs, but they were still below the 6.0% RSD allowed by US Pharmacopeia criteria.


Figure 7: Tabletability profile for microcrystalline cellulose–dibasic calcium phosphate formulation. (AUTHORS)
The tabletability profile (see Figure 7) shows that the tensile strength of all the tablet lots easily exceeded the desirable target crushing strength of 2.0 MPa. Also, the compactibility profile (see Figure 8) shows that the tablets achieved a tensile strength of 2.0 MPa at a solid fraction of approximately 0.80–0.81, indicating that strong bonds were formed at relatively low solid fractions. All formulations performed well, regardless of the mill type used or difference in particle-size distribution.


Figure 8: Compactibility profile for microcrystalline cellulose–dibasic calcium phosphate formulation. (AUTHORS)
MCC–lactose formulation. Weight variation for all the mill types was well below an RSD of 2.0%, and weight control is not considered a problem, regardless of the difference in particle-size distribution. Weight, thickness, and hardness values are listed in Table VII.


Figure 9: Tabletability profile for microcrystalline cellulose–lactose formulation. (AUTHORS)
The tabletability plot (see Figure 9) shows that the tensile strength of all the lots easily exceeded the desirable target of 2.0 MPa. However, the Gerteis milled formulation performed the best of all the lots. Its maximum tablet-crushing strength was ~0.5 MPa higher than the other mill types. The compactibility profile (see Figure 10) shows that the tablets achieved a tensile strength of 2.0 MPa when compaction was at a solid fraction of approximately 0.86–0.88. All formulations performed similarly, regardless of the mill type used and the difference in particle-size distribution, except for the Gerteis milled granulation.

Conclusions


Figure 10: Compactibility profile for microcrystalline cellulose–lactose formulation. (AUTHORS)
In general, the mill type used and resulting granulation particle-size distribution did not greatly influence the tabletability or compactibility of either placebo formulation. The MCC–DCP formulation demonstrated excellent tableting and compaction properties, regardless of the mill type used. Although a higher RSD for the tablet weight values using the Gran-U-Lizer was observed, it is considered acceptable. Adjustments to the Gran-U-Lizer parameters might make the particle-size distribution slightly lower and improve the granulation, tableting, and compaction performance.


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