Figure 2: Three-point beam bending test arrangement. (AUTHORS)
Tensile strength. The ribbon's tensile strength was determined using a three-point beam-bending tester (CT-5, Holland Instruments, Nottingham,
UK). Each ribbon sample was placed onto the two beams, separated by a known distance L. A force F was applied in the middle of the sample until the sample failed. Figure 2 demonstrates this test.
The tensile strength of the compact can be determined from the following relationship:
in which σT is fracture tensile strength, F is the load applied at fracture, W is the width of sample, L is the distance between beams 2 and 3, and t is the thickness of the sample.
Dry granulation by means of roller compaction. Ribbon from each formulation was roller compacted to an equivalent target solid fraction, tensile strength, and thickness
using the Gerteis Mini-Pactor. The ribbon was collected in approximately 1.0-kg portions throughout each compaction run to
ensure that the level of bypass remained consistent for each milling trial. It was important to the integrity of this study
that the ribbon not be collected in one large portion and that ribbon not be subdivided from one main ribbon supply because
this could potentially cause segregation of bypass (fines) during ribbon storage and produce inconsistent milling results.
Also, it was equally important that the bags of ribbon be numbered sequentially to easily identify at what time in the roller
compaction process a particular bag was compacted. The ribbon's physical properties were characterized from each 1.0-kg portion
collected to determine the consistency of the ribbon produced. Figure 3 illustrates the experimental plan used to produce
ribbon for milling.
Figure 4: Milling and tableting experimental plan. (AUTHORS)
Milling and tableting. The milling conditions selected for the Gerteis and M5A mill were based on previously established milling parameters used
for the size reduction of roller-compacted ribbon. The 0.8-mm screen size selected for both mill types produces satisfactory
granules for conventional IR tablet formulations consistently. The Comil speed was calculated to achieve a tip-speed equivalent
to that of the M5A mill equipped with a rotor bar. The larger mill screen size used for the Comil was based solely on availability.
The G040 (~1.0-mm) screen was the smallest rasping-style screen size available at that time from Quadro for the 197 Comil.
The differences in screen size between the Gerteis OG, M5A, and Comil are considered to have minimal effect on the final particle-size
distribution, given the considerable difference in mill designs. The Gran-U-Lizer milling conditions (e.g., number of passes
through the rolls, roller type, roller speed, and roller-speed ratio) were determined during a series of milling trials conducted
by MPE's engineering staff. Figure 4 illustrates the milling conditions used for each milling operation.
Thomas A. Vendola is a scientist in solids development, and Bruno C. Hancock is a research fellow in material sciences at Pfizer, Eastern Point Rd., Groton, CT 06340, tel. 860.441.4430, fax 860.441.3972.
Articles by Thomas A. Vendola