Measuring moisture content inline is a useful tool but the pharma sector has been slow to embrace its use. Dr Andrew Grady, market manager pharmaceuticals at NDC Infrared Engineering, reviews new developments that could see the technique more readily adopted
Moisture content is a critical attribute in fluid bed processes, relating directly to product quality: too wet or too dry and the tablet will not form properly. Pharmaceutical production managers and engineers checking moisture levels in powdered ingredients have traditionally relied on an offline Loss on Drying method. This can take many minutes to complete before confirmation is obtained that either the end-point has been reached, or that the batch requires further work, making the process inefficient, especially in terms of time, product quality and plant energy consumption.
However, the challenge to introducing an in-process alternative is that the measurement system must be both robust enough to meet the everyday process demands and be accurate and stable enough to be trusted as a closed-loop control solution. It simply must not compromise process integrity.
Other industrial sectors such as food production have long used Near-IR process analytical control solutions, and in particular, fixed filter-based near infrared (NIR) absorption sensors using up to 10 configurable wavelengths.
These have been successfully employed in thousands of locations in manufacturing facilities worldwide and are a very accurate method of measuring pre-defined components. They have been validated for their intended role to the extent that they warrant consideration by the pharmaceutical world as a viable alternative to an off-line measurement.
Furthermore, through suitable design of product-to-sensor interfaces for measurement robustness, these systems can control not just monitor a process, while introducing industry standard process connectivity options to the control suite. Their utilisation in very large numbers comes from the desire to optimise process efficiency, often with small additive returns that over a relatively short period of time yield significant financial savings.
For Fluid Bed Processes, steps have to be taken to avoid the historical problem of product fouling around the sampling window or probe. This has been resolved with the design of a new self-cleaning viewing window or "eye" which has been mounted into the side wall of the bowl. This eye is an adaptation of ball valve technology where a sapphire lens has been inserted into a stainless steel ball. A pneumatic actuator is used to rotate the eye, and the complete system is controlled by a sequencer which initiates opening for measurement and closing for cleaning. The cleaning process uses hot water from the pharmaceutical plant itself and the eye is dried in clean air.
Designed to form part of a fully validated process to meet the rigorous demands of the pharmaceutical industry, and launched under the name PharmaView, the first systems are already being used by a global pharmaceutical company. Suitable for new or existing manufacturing installations, here is a viable in-process alternative to Loss on Drying. The mounting element of PharmaView is specific to the fluid bed dryer so as not to compromise the process integrity.
The system complements the existing real-time outputs used to run a granulation suite by providing the key parameter of absolute moisture in the fluid bed dryer without the traditional stop/start sampling, giving consistent and repeatable results with a very high degree of accuracy.
Readings can now be used to explore and control accelerated drying programmes during the evaporative drying stages thus providing improved productivity.
This closed-loop process control solution for fluid bed processing, with its integral rotating eye (as shown in figure 1), enables the implementation of analytical methods in a manufacturing environment and is now available to the pharmaceutical world.
The mathematical processing of the data is carried out in the sensor head and the moisture reading is output in real-time (every 200ms) to the granulation suite DCS to generate drying profiles as shown in Figure 2. Sensors are delivered pre-calibrated requiring simple adjustment to the compendial method upon installation. The algorithms in the sensor incorporate a multi-wavelength balanced reference method to ensure readings are desensitised to natural product variations such as particle size and colour (figure 3).
The measurement of moisture in this way provides accuracy and repeatability, established at typically ±0.1% moisture (between 0-6% water content @ 2s) if adjusted against Karl Fischer Titration, as shown in figure 4.
Of equal importance, the presence of suitable documentation and design risk assessments make installation straightforward while ensuring efficient progress from installation qualification and operational qualification (IQ/OQ) through to performance qualification.
There is a strong business case for PharmaView. It reduces the need for reworking, while saving time, reducing energy consumption and cutting operative danger from drug exposure. By delivering no compromise measurements, which have been conceived from the outset as solutions to process needs, it fully overcomes the uncertainties arising from product fouling; improves batch-on-batch reproducibility and opens the way to speeding up the process.