At its in-house congress on “Pharmaceutical Hot Melt Extrusion”, held on April 15, 2010, Coperion, Stuttgart/Germany, provided around 100 guests from the pharmaceutical industry with a compact overview of this special, rapidly growing application. Pharmaceutical experts from both industry and science explained, by way of case examples and the results of R&D projects, the technology and vast area of application for hot melt extrusion in the pharmaceutical industry.
Coperion is regarded as one of the pioneers of hot melt extrusion. Its ZSK compounders are used in the pharmaceutical industry, for example, for the continuous production of tablet mixtures, transdermal patches with active ingredients or adhe-sives for medical appliances, e.g. ostomy bags. Further possible applications for hot melt extrusion are the manufacture of medical compounds with delayed ingredient release, processing of insoluble substances or substances that are difficult to dissolve, encapsulation and taste masking. To facilitate the further development of hot melt extrusion for pharmaceutical applications, Coperion has entered into an alliance with ISP Pharmaceuticals, Madrid, Spain. For its part, ISP contributes both its know-how in the field of excipients (e.g. polymers and disintegration agents) and its experience with formulations and material economy, while Coperion shares its expertise in the design and manufacture of extrusion systems for pharmaceuticals as well as its many years’ experience in process engineering.
One of the prerequisites for hot melt extrusion in pharmaceutical applications is the use of an extrusion line that is in keeping with good manufacturing practices (GMP). This requirement is fully met by the special pharmaceutical version of Coperion’s ZSK Megacompounder Plus: it is self-cleaning and has virtually no dead spots in the entire system. All parts that come into contact with the product are manufactured from proven materials with specially treated surfaces. The system uses only FDA-approved oils and lubricants. In addition, the extruder meets the very stringent workplace safety requirements of the pharmaceutical industry. Congress participants were able to gain a practical impression of these special features during a demonstration of hot melt extrusion in Coperion’s test lab, when organic pigments were worked into matrix polymer.
Hot melt extrusion technology is used to mix active pharmaceutical ingredients (APIs) into a matrix. To this end, the starting materials, i.e. the APIs, the matrix substances and the additives, are fed continuously in exactly the required quantities via gravimetric feeding systems into the process section of the ZSK Megacompounder Plus, where they are melted with the aid of the co-rotating twin screws and then gently mixed and homogenised at low temperature in only a few seconds. The screw shafts feature different, process-optimised screw flights for each extruder zone. If required, further solid or liquid substances can be fed downstream into the extruder barrel via lateral feeding devices. A vacuum venting system is often installed just upstream of the discharge section in order to release trapped air, volatiles and/or solvents and thus obtain a bubble-free melt. The finished compound can then be directly extruded and pelleted by the ZSK Megacompounder Plus via an extrusion die plate or further processed in a downstream calender.
The entire extruder system of the machine, comprising the extruder barrel, the screw and the screw flights, is of modular design.
Compared with conventional processes, continuous hot melt extrusion affords the manufacturer many advantages:
- It is also suitable for processing substances that are insoluble or very difficult to dissolve in water, as a stable and uniform dispersion of the substances is obtained in the matrix during the compounding process.
- It can increase API content and also improve the bioavailability of the APIs.
- It is a solvent-free process, thus waiving the need for certain production stages, e.g. drying.
- Its efficient mode of operation ensures very high homogeneity, while the short residence time and low operating temperature ensure gentle compounding.
- It is suitable for the production of medical masses with tailored or delayed release systems.
These processing advantages are complemented by a great many benefits in terms of the actual practical application of hot melt extrusion. Coperion’s compounders for hot melt extrusion are distinguished by their economic efficiency and, owing to their continuous mode of operation, their typical reproducibility of quality and exact adherence to formulation. The machine control system, with its online monitoring capability, ensures accurate observation of process parameters and generates the necessary production records. Moreover, thanks to its compact design, the ZSK Megacompounder Plus takes up only negligible floor space. As the twin screws in the ZSK are largely self-cleaning, changing over from one formulation or product to another can be effected without difficulty. The modules of the compounding system are clearly arranged, easy to operate and readily accessible for cleaning and maintenance purposes.
To allow users to optimally exploit the aforementioned advantages of hot melt extrusion, Coperion offers comprehensive backup through its specialised process engineers. Their know-how enables reliable process control and accurate adaptation of process parameters to other sizes of machine. Coperion can also draw on years of experience in mathematical modelling of the extruder’s processing parts, thus ensuring an accurate forecast of the process when it comes to using the compounder for new applications.