We sit down with Dirk Leister, technical marketing manager, process and pharma extruders for Thermo Fisher Scientific, to find out more about hot melt extrusion and the company’s new automated, integrated system designed for continuous production of drug implants.
End-to-end
Q. What is hot melt extrusion (HME) in a nutshell?
Based on well-established screw technology that transports and compounds material ingredients to the point of extrusion, melt extrusion has been in use for several decades in the formulation of plastics, rubbers, foods and many other materials. Regarding the possibilities of pharmaceutical processing using twin-screw instrumentation, not only is HME an option, with its range of possible applications, but wet extrusion and granulation processes can also be accomplished with today’s modern twin-screw extruders.
Thermo chart
Q. How is HME advantageous in drug development?
In the 1980s, HME was considered a promising new technology used to overcome solubility issues for newly developed drug molecules. Soon after market introduction, the first commercially available medicine manufactured with HME became available for immunodeficiency treatment. Since then, the technology has developed further and solved many formulation challenges in the fields of controlled and modified release, taste-masking, prevention of drug abuse and, more recently, for drug delivery systems such as co-extrudes and subcutaneous implants.
HME has become a versatile tool for modern formulation scientists. If we consider that continuous manufacturing is the next big development step in pharmaceutical processing, the role of pharmaceutical twin-screw processes will significantly increase for certain applications, such as continuous granulation.
Q. Can the physical properties of compounds throw up challenges in HME?
Some materials being used in the HME process can be sticky, cohesive or sensitive to electrostatic. Preventing segregation and ensuring precise dosing of those compounds is key for a high-quality end-product.
With extensive experience enabling our customers to develop pharmaceutical extrusion processes, Thermo has successfully completed a number of projects involving ‘challenging’ compounds. We have been able to help our customers design robust processes, even when one or two of the ingredients of the formulation exhibit demanding physical properties.
Q. Could you briefly run through the essentials of the new Pharma mini implant line and how it will benefit pharma manufacturing?
Based upon our proven and successful Thermo Scientific Pharma mini HME twin-screw micro compounder, the Thermo Scientific Pharma mini implant line is an automated end-to-end solution for developing and commercial manufacturing of injectable drug delivery systems that meet cGMP and FDA requirements.
A closed-loop control and recording system ensures precise, secure operation and a compliant product as well as process documentation. A laser-based measuring and monitoring device and high-precision cutting are designed to ensure that all manufactured implants are fully in spec.
The Pharma mini implant line is designed to help pharmaceutical manufacturers improve product quality while minimising development time.
Q. What is the significance of end-to-end manufacturing?
When used for commercially manufactured drug delivery devices, precisely controlled end-to-end manufacturing is important because it documents all relevant parameters for compliant manufacturing. When carefully applied, end-to-end manufacturing enables product release without further testing or analysing — the equivalent of real-time release of a product. This is a huge advantage for drug producers.
The Thermo Scientific Pharma mini implant line encompasses all necessary technical features to support end-to-end manufacturing. If the process designed by a drug producer also complies with the regulations, the drug producer can realise much faster time-to-market for new formulations.
Q. What advantages can manufacturers expect from an implantable drug delivery system over more conventional delivery forms?
Implantable drug delivery systems offer several advantages over conventional oral dosage forms. Implants allow site-specific drug administration where the drug is needed most. Examples include implants used in the treatment of prostate or breast cancer. This also allows for lower doses of the drug, minimising unwanted side effects.
Dirk Leister, technical marketing manager, process and pharma extruders for Thermo Fisher Scientific
Dirk Leister
As implantable devices allow for sustained release of an API, it removes the burden to take multiple pills or injections per day. Perhaps the most important advantage is patient compliance, as some clinical patterns make it difficult or impossible for the patient to adhere to the treatment schedule.