Improved Understanding and Control of Fluidised Bed (Wurster) Coating Process
Many oral dose medicinal products are formulated to enable modified or extended release of the active ingredient. Multi-step Fluid Bed (Wurster) Coating processes are routinely used to layer pellets or beads with a target amount of drug, functional or seal coat to achieve the desired release profile during formulation. Process Analytical Technology or “PAT” allows for process measurements in situ with instant access to data which facilitates rapid decisions during product development and manufacture. Monitoring particle size and distribution during process runs can help demonstrate that the substrate is coated evenly and within the required coating thickness range. The ability to monitor particle growth in real time allows a deeper understanding of the process and aids in the development of an improved process control strategy.
Waiting for Dissolution test results?
Dissolution is the QC test for development and manufacture of solid oral dose drug product including controlled release formulations. Dissolution, however, cannot be directly measured in-line due to the long duration of the analytical test. It can, therefore, take several days or weeks until dissolution test results are available which causes delays in process development and adds considerable time to commercial manufacture cycle time unless it is decided to proceed at risk with these activities.
Could Real-Time in-line PSD measurement during processing accurately Predict Off-Line Dissolution Test Results?
While direct measurement of dissolution performance in-line may not be practical to implement there is huge potential to significantly reduce product development and production cycle times with a real-time test that can accurately predict the off-line dissolution test results of a modified release product.
In order to have practical utility, the in-line system would have to accurately determine coating thickness of a coated particle “in-process” and then the results should correlate functional coating thickness with the dissolution profile.
- Is there a correlation between functional coating thickness and dissolution profiles?
- Is Real-time dissolution prediction of a coating process using particle size data a viable control method?
- Will prediction data be reliable enough to use during process development, optimisation, scale-up and transfer?
- Is there potential for including particle size PAT as part of an improved process control strategy?
- Can in-line particle measurement help reduce process variability, processing or cycle time?
New Data Demonstrates Potential of the Approach
New Data from a series of experiments conducted by industry leaders Glatt, Colorcon and Innopharma saw Colorcon Suglets® with Chlorpheniramine Maleate coated with Surelease® and Opadry®EC functional coatings to obtain modified release characteristics in a Glatt GPCG2 lab-scale fluid bed system. Measurement was then performed using an Innopharma Technology Eyecon2™ particle analyser. The results were then analysed to determine if there is a good correlation between functional coating thickness and the dissolution profile. To Download the application click here
Practical Implementation on Popular Fluid Bed Systems
Innopharma Technology and Glatt have collaborated to develop Eyecon2 hardware interface and control system integration solutions for the most popular Glatt machines from the GPGC2 at lab scale to scale up and production machines. This facilitates rapid set up to generate real-time in-line PSD data for deeper process understanding during QbD/DoE development and scale up activities and for process control during manufacture where required.
A Glatt GPCG2 with Wurster insert was used for the process work described and can be specified with Wurster product inserts configured with viewing ports compatible with Eyecon2 and positioned for optimal measurement of particle size during processing. For more info please click on the image
Scale Up and Production
Glatt machines like the GPCG Range can be specified with viewing ports optimised for use with Eyecon2. Existing customers can order a replacement viewing port to install on their existing equipment where required allowing the use of Eyecon2 from lab scale to scale up to commercial manufacture equipment. Contact Innopharma Technology or Glatt to assess the suitability of viewing ports on specific machines already installed.
Integration with Machine HMI and control System
EyePASS, Eyecon’s control, acquisition and reporting software can be integrated with machine HMI and control systems such as GlattView allowing access to real-time in-line PSD information and integration with machine and process parameter data. EyePASS can also integrate with typical historians used in development and manufacture.