Addressing Segregation of a Low-Dosage Direct Blend - Pharmaceutical Technology

Latest Issue

Latest Issue
PharmTech Europe

Addressing Segregation of a Low-Dosage Direct Blend
The authors modified equipment and the manufacturing process to re-establish content uniformity among tablets.

Pharmaceutical Technology
Volume 35, Issue 2, pp. 78-82

Process and equipment modifications

Modifications to the blender-to-bin transfer step. The blender-to-bin transfer step for the first demonstration batch consisted of an uncontrolled free fall from the blender into the bin, likely resulting in fluidization and dusting segregation. To reduce the likelihood of segregation during the blender-to-bin transfer step for the second demonstration batch, a flexible sleeve, or sock, was designed to control and reduce the transfer rate from the blender and minimize the free fall of the material during transfer. The customized sock had a conical section at the top that converged from the larger V-blender outlet (8-in. diameter) to a smaller diameter (i.e., 4 in.) to provide greater control of the material and reduce the free fall of material into the bin. In addition, the blender valve was throttled during discharge (as high as 10% open) so that the material could deaerate within the sock before the sock was lifted from the top surface of the material to transfer it into the bin. Based on the stratified blend samples collected within the bin after filling (RSD = 1.0%, n = 10 samples), these process modifications were successful in minimizing segregation during this transfer step.

In addition to modifying the process equipment used for the blender-to-bin transfer step, the cone-in-cone bin was expected to provide mass flow and was used for the second demonstration batch. Visual observations of the material discharge from the bin during the second demonstration batch confirmed mass-flow discharge, as predicted by the bench-scale flow-properties tests conducted beforehand.

Modifications during bin-to-press transfer. Segregation also could occur during the bin-to-press transfer step and contribute to the CU trending observed in the first demonstration batch. The transfer chute used for the first demonstration batch consisted of large-diameter (i.e., 8-in.) tubing without any valves to reduce the free fall of material or venting to reduce the air counterflow up through the powder as the chute is filled. Since air counterflow during free fall as the chute is filled can result in fluidization and dusting segregation, thus carrying drug-rich fines back up into the bin above, a new transfer chute design was used for the second demonstration batch. The new transfer chute consisted of the following parts:
  • A mass-flow conical reducer at the top of the chute and small-diameter (i.e., 4-in.) tubing to reduce the displaced air and counterflow during filling
  • Two butterfly valves to reduce the free fall height during filling
  • A passive filter vent to allow displaced air during filling to exit the chute rather than conveying back up through the blend and causing segregation.

Figure 3: Tote-bin and transfer-chute modifications from (a) demonstration batch #1 in a bin-to-press feed system and (b) demonstration batch #2 in a modified bin-to-press feed system after process and equipment modifications. (ALL FIGURES ARE COURTESY OF THE AUTHORS)
The modifications to the bin and transfer chute design from the first demonstration batch to the second demonstration batch are shown in Figure 3.


blog comments powered by Disqus
LCGC E-mail Newsletters

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

Which of the following business challenge poses the greatest threat to your company?
Building a sustainable pipeline of products
Attracting a skilled workforce
Obtaining/maintaining adequate financing
Regulatory compliance
Building a sustainable pipeline of products
Attracting a skilled workforce
Obtaining/maintaining adequate financing
Regulatory compliance
View Results
Eric Langer Outsourcing Outlook Eric LangerBiopharma Outsourcing Activities Update
Cynthia Challener, PhD Ingredients Insider Cynthia Challener, PhDAppropriate Process Design Critical for Commercial Manufacture of Highly Potent APIs
Jill Wechsler Regulatory Watch Jill Wechsler FDA and Manufacturers Seek a More Secure Drug Supply Chain
Sean Milmo European Regulatory WatchSean MilmoQuality by Design?Bridging the Gap between Concept and Implementation
Report: Pfizer Makes $101 Billion Offer to AstraZeneca
Medicare Payment Data Raises Questions About Drug Costs
FDA Wants You!
A New Strategy to Tackle Antibiotic Resistance
Drug-Diagnostic Development Stymied by Payer Concerns
Source: Pharmaceutical Technology,
Click here