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


Table IV: Microcrystalline cellulose–dibasic calcium phosphate granulation particle-size (μm) and flow properties.
Milling. Both formulations were milled using the 1.0-kg bags of ribbon collected during the roller-compaction process. Because individual bags of ribbon were used and the bypass level was well controlled, it can be assumed that any difference in the postmilling fines level was generated by the milling process and not a result of segregation during handling of the ribbon. Also, because the ribbon sample bags were numbered during roller compaction, the results of each milling trial can be directly compared with ribbon solid fraction, tensile strength, and thickness values. One milling for each formulation was performed using each of the mill types.


Table V: Microcrystalline cellulose–lactose granulation particle size (μm) and flow properties.
One major difference between the conventional mill types and the Gran-U-Lizer was the number of passes necessary to achieve the desired particle-size distribution. The conventional mill type required only one pass to achieve the desired reduction in particle size. The Gran-U-Lizer required several passes using different roller styles, roller speeds, and roller gaps. According to MPE, multiple passes produce a gradual reduction in particle size and thus a low level of fines.


Figure 5: Microcrystalline cellulose–dibasic calcium phosphate placebo particle-size distribution. (AUTHORS)
Granule physical property data. Particle-size distribution. Tables IV and V show the results of laser-diffraction particle-size analysis using a disperser (HELOS/RODOS, Sympatec, Clausthal-Zellerfeld, Germany). The particle-size distributions show that the Gran-U-Lizer produced the largest particle size of all the mills tested. However, all the milled formulations had similar distributions, as demonstrated in Figures 5 and 6. In addition, the distributions for both formulations were broad, regardless of the mill type used.


Figure 6: Microcrystalline cellulose–lactose placebo particle-size distribution. (AUTHORS)
Flowability. The MCC–DCP formulation exhibits excellent flowability across all mill types, while the MCC–lactose formulation exhibits lower (good) flowability, with the exception of the Gran-U-Lizer, which demonstrated excellent flow based on a flow function coefficient value of 10.1 (4). However, the larger particle size of the Gran-U-Lizer granulations did not substantially improve the flowability of either formulation.


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.
28%
Oversee medical treatment of patients in the US.
12%
Provide treatment for patients globally.
9%
All of the above.
45%
No government involvement in patient treatment or drug development.
7%
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
Seven Steps to Solving Tabletting and Tooling ProblemsStep 1: Clean
Legislators Urge Added Incentives for Ebola Drug Development
FDA Reorganization to Promote Drug Quality
FDA Readies Quality Metrics Measures
New FDA Team to Spur Modern Drug Manufacturing
Source: Pharmaceutical Technology,
Click here