The following is included in this e-tech newsletter:

  • 8th annual Pharmaceutical Extrusion Seminar to be held June 12-13, 2013
  • Examples of TPU processes using twin screw extruders
  • Technical paper: Twin Screw Extruder Developments for Consistent/Repeatable Concentrates  (and why/how plastics and pharmaceutical manufacturing operations are learning from each other)
  • Featured model: ZSE-27 MAXX modular/high speed twin screw extruder
  • Leistritz participates in Twin Screw Extrusion Seminar @ ICIPC in Colombia
  • Upcoming exhibit/presentation schedule

Leistritz will host the 8th annual Pharmaceutical Extrusion Seminar on June 12-13, 2013, which will combine classroom sessions and twin screw extrusion demonstrations.  This “hands-on” seminar starts with the basics and explains why extrusion is an ideal technology to comply with the FDA’s Process Analytical Technology (PAT) initiative, as well as presenting cutting-edge extrusion technologies being developed and utilized for a variety of dosage forms.  Anyone involved with pharmaceutical extrusion will benefit by attending this program.  Some of the topics include:

  • Twin screw extrusion theory and design
  • Advantages of continuous extrusion as compared to batch processes
  • Staging of unit operations in an extrusion system to facilitate continuous compounding
  • Mixing techniques for poorly soluble and heat/shear sensitive API’s
  • Upstream equipment designs for feeding, material handling and containment
  • Scale-up of the extrusion process- R&D, pilot scale and production
  • Downstream systems for pelletizing, films, molding and shape extrusion
  • Cleaning and maintenance of extrusion equipment in a cGMP environment
  • Equipment and process validation practices and documentation
  • Control issues pertaining to CFR 21 part 11 compliance
  • New emerging extrusion technologies, i.e. supercritical foaming and coextrusion
  • Selection of excipients for processing API’s

 

“Hands-on” demonstrations at Leistritz process laboratory will include:

  • nano-16 twin screw extrusion system processing 50 gram batch samples
  • Film/lamination extrusion system  as used for transdermal or dissolvable film applications
  • Micro-pelletization extrusion system producing ½ mm pellets for direct capsule filling
  • Melt granulation extrusion technology for high potency/strength tablets
  • Extrusion system for compounding heat/shear sensitive API’s via hot melt extrusion

Classroom sessions are held at the Holiday Inn Select in Clinton, NJ, and extrusion demonstrations at the nearby Leistritz Process Laboratory in Somerville, NJ.

In addition to Leistritz staff, outside industry experts will contribute to the program content.

Price to attend:  Early registration, if received by May 15, 2013, is $820; after this date cost is $920.

For latest program details see this link:  http://www.alec-usa.com/PES2013.htm.

To register for this program contact Sarah Scovens at 908/685-2333, x614 or e-mail sscovens@alec-usa.com.

To download a registration form for the Pharmaceutical Extrusion Seminar

Examples of Polyurethane Processes using twin screw extruders

Twin screw extruders (TSE’s) are used to process virtually every type of plastic that is used today, including many thermoplastic polyurethane (TPU) formulations. TPU’s range from being hard like a thermoplastic to being flexible like an elastomer, with the properties determined by the balance between the isocyanates, polyols, chain extenders and catalysts in the formulation.   TPU’s tend to be heat and shear sensitive, which must be accommodated in the TSE design, as well as soft and sticky, which may require special downstream system considerations. 

The following summarizes a few examples of TPU TSE systems:

TPU reactive extrusion system with underwater pelletization:   Liquids can be metered separately or pre-mixed in a reaction vessel prior to the TSE to increase the residence time for the reaction. Reaction cylinders and high speed mixers for monomer mixtures and pre-polymers are commonly integrated into the design. 

Liquid feed streams are metered into the TSE by precision injection pumps utilizing loss-in-weight monitoring/control to maintain the correct stoichiometry.  The length to diameter (L/D) ratio is typically between 32 and 52/1 to allow for residence times in the 30 seconds to 6 minute range. Intimate mixing with a low peak shear is managed by the selection of distributive mixers, such as “combing elements”. Since polyols and isocyanates are immiscible before the reaction occurs, this issue must be addressed in the TSE screw design. 

dsc00021
Close-up “combing” distributive mixing elements

The TSE screw design, process section temperatures and operating conditions all play a role in the final molecular weight and molecular weight distribution.  The feed rate versus TSE screws rpm manages the required residence time and residence time distribution to facilitate the reaction.  The stress rates and temperatures also play roles in controlling the reaction and urethane formation.  Volatiles are removed by vacuum venting, which can be staged.

The TSE is then mated to an underwater pelletizer.   A melt flow diverter may be utilized, and the start-up sequence of the extruder, cutter and water flow is managed by a PLC for consistent and repeatable start-up and process management.  Gear pumps can be integrated into the system if elevated pressures are a requirement, as would be the case for micro-pellets (less than 1 mm) production or if ultra-fine filtration is opted.   


TSE TPU reactive extrusion system with underwater pelletization

Radiopaque TPU direct sheet extrusion:  Dried TPU pellets are metered into the TSE by a loss-in-weight (LIW) feeder with a nitrogen purged hopper.  Additives are also metered into feed throat by a 2nd LIW feeder.  Solids conveyance and melting occurs early in the process section and barium/bismuth is then introduced into the melt stream by a side stuffer that “pushes” the radiopaque filler into the melt stream.   The filler is metered to the side stuffer by a 3rd LIW feeder. The materials are then mixed, vacuum vented and discharged from the TSE.   For high-level filler levels (i.e. 80%) multiple side stuffers and an extended L/D may be required.

A gear pump at the discharge of the TSE builds/stabilizes pressure to the die.  The die/downstream system is the same as if a single screw extruder was the melt delivery mechanism.  The same process sequence applies to other extruded parts, such as a film, tube, filament, fiber or profile.  


TSE direct extrusion sheet system

TPU/supercritical CO2 foamed profile: The TPU and additives are metered into a TSE by LIW feeders and melted/mixed.  Dynamic seals are integrated into the screw design to accommodate the high-pressure injection pressures inherent with a supercritical fluid.  One-piece barrel sections can be specified to eliminate the possibility of leakage at the barrel junction flanges. The injection system is equipped with a precision injection pump with chilled/temperature controlled plumbing connections.

49003
TSE supercritical injection system

Once the supercritical fluid is injected it is intimately mixed with the molten TPU via high division distributive mixers that minimize viscous heating. The latter part of the crew design then utilizes low energy input pumping elements to allow the TSE barrel sections to serve as a heat exchange device to help cool the melt.  At lower throughputs, it may be feasible to cool the extrudate and pressurize the die directly from the TSE.  In this instance a longer L/D (i.e. 52/1 L/D) may be required.  At higher rates, for improved cooling, a single screw pump is specified, which is essentially an oversized, slow turning single screw extruder that provides process length to cool the melt and pressurize the die.

Editor’s note:  See Szycher’s Handbook of Polyurethanes, Second Edition (CRC Press) for additional information on all technical aspects relating to TPU processing and properties.

Technical Paper:  Twin Screw Extruder Developments for Consistent/Repeatable Concentrates (why plastics and pharmaceutical manufacturing operations
are learning from each other)

Twin screw extrusion has been an established technology for producing color concentrates for many decades.  Prior to the use/acceptance of twin screw extruders (TSE’s), batch mixers and single screw extruder were the mixing devices of choice.  In the last dozen years an analogous evolution has occurred in the pharmaceutical industry, as twin screw extrusion has emerged as a viable platform to mix active pharmaceutical ingredients (API’s) with polymers and additives that serve as binders.   Just like plastics compounding, the TSE is utilized as a continuous mixer to extrude a high-quality, consistent drug delivery mechanism. 

The basic design of a twin screw extruder, the mixing mechanisms and staging of unit operations are also virtually identical for concentrate and pharmaceutical applications.  TSE process technologies proven in industrial masterbach production settings can often be quickly implemented for a pharmaceutical process- the TSE process is a known quantity.  


nano-16 twin screw extruder process section

Equipment validation documentation related to equipment installations into a pharmaceutical class environment is more intensive as compared to a typical plastics machine.  Detailed/project specific documentation packages for the Factory Acceptance Test (FAT), Installation Qualification (IQ) and Operational Qualification (OQ) are required, which adds months of time and effort to the installation and commissioning of the equipment.

There are also cGMP guidelines for cleaning pharmaceutical class TSE systems. For instance, the equipment must be cleaned at appropriate intervals and written procedures are required that must be specific and detailed.  Cleaned equipment must be protected from contamination prior to use and inspected for cleanliness before utilization. Records of cleaning and inspection must be kept, and the time between end of processing and cleaning steps must be recorded.

Due to the regulatory requirements inherent with pharmaceutical manufacturing, the TSE cell necessitates a more documented approach as compared to standard practices in the plastics industry. It is not the author’s suggestion that FDA guidelines and regulations should be strictly applied to the manufacture of plastics/concentrates, but that it may be useful to audit pharmaceutical practices and selectively implement those procedures that are practical and useful to help make a more consistent, repeatable end-product.

To download a complete copy of this paper ..

  

Featured HSEI TSE: ZSE-27 MAXX twin screw extruder

The ZSE-27 MAXX is ideal for pilot scale development and small-scale production….it commonly produces 300+ lbs/hr of color masterbatch and similar products.


ZSE-27 MAXX with side stuffer, swing gate die and vacuum pump

Some basic specifications are as follows:

Screw diameter 28.3 mm
Flight depth 5.6 mm
OD/ID ratio 1.66
MAXX torque 304 NM
Weight

1000 kgs (approx.)

Miscellaneous Based mounted electricals/HMI controls, roll-around design

To download a ZSE-27 MAXX specification sheet

Leistritz participates in Twin Screw Extrusion Seminar @ ICIPC in Colombia

On June 7-8, 2012 Leistritz participated at the Twin Screw Extrusion Seminar hosted by the prestigious Instituto de Capacitación e Investigación del Plástico y del Caucho (ICIPC) in Medellin, Colombia.  Charlie Martin and Augie Machado gave presentations on behalf of Leistritz.  Dr. Costas Gogos of the Polymer Processing Institute also contributed.  The program was organized by Dr. Maria del Pilar Noriega, the Director of ICIPC, who also presented at the event, along with other ICIPC staff.

The 60+ attendees had the opportunity to tour the extensive ICIPC process and analytical laboratories, and participate in a “live” ZSE-27 twin screw extrusion demonstration.

Leistritz will also be participating at the upcoming ICIPC Colloquium on March 18-19, 2013 in Medellin.   For additional details see http://icipc.org.


Charlie Martin (Leistritz), Dr. Costas Gogos (Polymer Processing Institute), Dr. Maria del Pilar Noriega (Director, ICIPC), Dr. Alberto Naranjo (past Director, ICIPC) and Augie Machado (Leistritz)
at the ICIPC Twin Screw Extrusion Seminar

2013 Industry events where Leistritz will participate

Jan. 28-31 Next Generation Bio-Based Chemicals, San Diego, CA
Jan. 29-31 AMI Thermoplastic Concentrates 2013, Coral Springs, FL
Feb. 12-14 Plastec West 2013, Anaheim, CA
Feb. 24-27 SPE 2013 International Polyolefins Conference, Houston, TX
March 12-15 Plastimagen 2013, Mexico City, Mexico
March 18-19 ICIPC Colloquium 2013, Medellin, Colombia
April 22-24 SPE ANTEC 2013, Cincinnati, OH
May 7-8 AMI Bioplastics Compounding & Processing 2013, Miami, FL
June 12-13 Leistritz Pharmaceutical Extrusion Seminar, Clinton, NJ
July 21-24 CRS 2013, Honolulu, Hawaii
Sept. 22-24 SPE CAD RETEC 2013, Baltimore, MD
Oct. 16-23 K 2013, Dusseldorf, Germany
Nov. 10-13 AAPS Meeting & Exposition 2013, San Antonio, TX
Dec. 4-5 Leistritz Twin Screw Extrusion Workshop, Clinton, NJ

To receive more information on anything contained in this newsletter e-mail
sales@alec-usa.com
or visit http://www.alec-usa.com/tsrpt01-2013.htm



169 Meister Ave.
Somerville, NJ, 08876, USA
ph: 908/685-2333
e-mail: sales@alec-usa.com
www.leistritz-extrusion.com