Continuous Mixing of Solid Dosage Forms via Hot-Melt Extrusion - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

Continuous Mixing of Solid Dosage Forms via Hot-Melt Extrusion
The author describes the benefits, processes, and practicality of using hot-melt extrusion to mix active pharmaceutical ingredients with pharmaceutical-grade polymers.


Pharmaceutical Technology
Volume 32, Issue 10, pp. 76-86


Figure 11 (All figures are courtesy of the author.)
Pelletization is a downstream process for hot-melt extrusion where the melt stream is pumped through the die, cooled and formed into a pellet, typically between 0.5 and 5 mm. In strand pelletization, "spaghetti" strands are extruded and cooled on a stainless steel or FDA-approved plastic-belt conveyer. The feedrolls of the pelletizer pull the strands and push them into the cutting assembly where cylindrical pellets are produced. Die-face pelletization is also common, where the pellets are cut at the die face and conveyed/cooled by various methods, including chilled air chimneys and vibratory towers. Because many pharmaceutical formulations tend to smear at the die face, this method should be tested prior to implementation. Smaller pellets can be used for direct capsule-filling, and in-line spheronization is also possible (see Figure 11).

For the production of flat film or sheets such as those used in transdermal or dissolvable-film applications, the process melt material is distributed in the die and cooled on rolls. The roll surface is maintained at the desired temperature by pumping a liquid (typically water or oil) through internal cooling channels. The molten material solidifies onto the roll as it cools. Take-off units are available in several different roll-stack configurations such as vertical and/or horizontal arrangements. For many flat products, the nip force across the roll face is used to "squeeze" the extrudate between the rolls. Unwind stations can be used to laminate the film onto a substrate. The final product is then either wound or cut to length.

Shape extrusion occurs when the process melt is directly extruded into a part with specific dimensions. The extrudate can be a simple rod, or complex shape, referred to as a "profile." The extruded profile is formed in the die, sized by calibration tooling, and then conveyed and supported on a conveyer with auxiliary air cooling devices. A belt puller then feeds the product to an on-demand or flywheel-type cutter. In this manner, for example, a 3 mm-diameter by 1 mm-length tablet might be produced.

Summary

Twin-screw extruders are becoming the manufacturing methodology of choice to continuously mix APIs with pharmaceutical grade polymers. Twin-screw extruders are highly flexible and efficient mixing devices suited for producing wide ranging pharmaceutical products that demand consistency and high quality. Understanding the extrusion process, as well as integration of the machine system, is necessary to ensure content uniformity for both compounds produced via hot-melt extrusion.

Charlie Martin is a general manager at Leistritz North America, tel. 908.685.2333, ext 616,




What would you do differently? Email your thoughts about this paper to
and we may post them to the site.

Additional reading

1. I. Ghebre-Sellassie and C.E. Martin, Eds., Pharmaceutical Extrusion Technology (Marcel-Dekker, New York, 2003).

2. D.B. Todd, Ed., Plastics Compounding Equipment and Processing (Hanser, New York, 1998).

3. J. Wagner and J. Vlachopolous, Eds., The SPE Guide on Extrusion Technology and Troubleshooting (Society of Plastics Engineers, Brookfield, CT, 2001).

4. S. Nowak, "Feeders in Milling and Micronization of Pharmaceutical Powders," Chem.Info (Advantage Business Media, Aug. 2006), available at www.chem.info accessed June 11, 2008.

5. M.M. Crowley et al., Eds., Drug Development and Industrial Pharmacy (Informa Healthcare, USA, 2007).


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.
30%
Oversee medical treatment of patients in the US.
9%
Provide treatment for patients globally.
8%
All of the above.
45%
No government involvement in patient treatment or drug development.
8%
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
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
From Generics to Supergenerics
Source: Pharmaceutical Technology,
Click here