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

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

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


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 σ T 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.

Experimental plan


Figure 3: Roller-compaction experimental plan. (AUTHORS)
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.


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
What role should the US government play in the current Ebola outbreak?
Finance development of drugs to treat/prevent disease.
Oversee medical treatment of patients in the US.
Provide treatment for patients globally.
All of the above.
No government involvement in patient treatment or drug development.
Finance development of drugs to treat/prevent disease.
26%
Oversee medical treatment of patients in the US.
12%
Provide treatment for patients globally.
10%
All of the above.
43%
No government involvement in patient treatment or drug development.
10%
Jim Miller Outsourcing Outlook Jim MillerCMO Industry Thins Out
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerFluorination Remains Key Challenge in API Synthesis
Marilyn E. Morris Guest EditorialMarilyn E. MorrisBolstering Graduate Education and Research Programs
Jill Wechsler Regulatory Watch Jill Wechsler Biopharma Manufacturers Respond to Ebola Crisis
Sean Milmo European Regulatory WatchSean MilmoHarmonizing Marketing Approval of Generic Drugs in Europe
FDA Reorganization to Promote Drug Quality
FDA Readies Quality Metrics Measures
New FDA Team to Spur Modern Drug Manufacturing
From Generics to Supergenerics
CMOs and the Track-and-Trace Race: Are You Engaged Yet?
Source: Pharmaceutical Technology,
Click here