Lighthouse Probe™ - online measurement

概述
GRANULATION endpoint detection
MOISTURE MEASUREMENT

Compact & Cleanable In-process Optical Probe

The Lighthouse Probe™ enables PAT

The biggest flaw of optical spectroscopy is the dependency on a clean observation window. When this so-called window fouling occurs during process, it will eventually lead to wrong analysis results, unwanted process stops and bad product quality. Since on-line and in-line optical analysis becomes more and more important today, reliable and robust systems, capable of overcoming this flaw are needed.

Though various vendors made attempts to overcome the issue using window heating and blow off systems, none of these ‘solutions’ seemed to work over longer time span. And all of them had the same flaw: once the fouling occurred, there was no way of recovering. To ensure an optical detection that can overcome these issues and check it’s status during the process, the Lighthouse Probe™ was developed. The probe has window cleaning capabilities and an internal reference to overcome a second frequently encountered issue namely reference contamination. Both these functions can be used in process without breaking containment.

The Lighthouse Probe™ comes in 2 different types:

Manual probe
Automated CIP probe

The probes can be upgraded from manual to automated CIP alongside with the development of your product from laboratory to production. They can be delivered matching a variety of spectrometers.

Benefits

Time savings: The Lighthouse Probe™ can be used for realtime release.
Resources savings
Materials savings

Example:

During the FAT of a Consigma™ tableting line, the Lighthouse Probe™ was used for on-line moisture analysis: The moisture of the final granulate was available in real time while off-line lab analysis took one week to analyze only one third of the samples (time savings).

The difference in resources savings consumption during that same FAT was 2 man-week of lab analysis (and lab-consumables).

Because of the direct availability of the analyzer data, deviation from the desired quality is detected immediately and corrections were made based on that data and the process moved back to optimal quality before even going out of spec. The offline analysis of one sample took 12 minutes (optimal case) so the minimal waste in case of a bad result in case of off-line analysis is 5 kg (throughput of the machine being 25kg/hr) (material savings)

Summary

The Lighthouse Probe™ provides:

In-process window cleaning at any time.
Recalibration at any time during the process
Full CIP of wash housing and seal
Always a clear view inside, even in difficult conditions

Future developments

The Lighthouse Probe™ will develop further to a platform enabling PAT. Various developments are taking place simultaneously and more and more suppliers of optical analytical methods are joining.

Ongoing developments:

Integration in data management systems such as SynTQ^® and SIPAT
Combination of different optical techniques
Imaging systems
Increased measurement spot size

Lighthouse Probe™ - DAD

High Shear Granulation Endpoint Detection

Online Process Monitoring

Suitable for monitoring blend homogeneity, moisture, density, by correlating spectra, physical granule properties by correlating scattering effect
More consistent batches resulting in better tablets
Non-destructive and direct online analysis of granule quality
Very fast spectroscopic technology using Diode Array Detector (other spectroscopic technologies possible)
Reliable and robust process interfacing to guarantee representative measurements.

Main Benefits

NIR spectra contain physical and chemical information about the measured product, allowing good correlations with traditional granulation parameters like density, particle size etc.
Using the Lighthouse Probe™ – DAD sensor for endpoint determination will give more consistency between batches in granule properties, enabling optimisation of subsequent processing steps.
Less waste thanks to a more consistent quality of the batches. Real-time availability of the product data like moisture content and density will decrease risks and reduce waiting time for the finished batch to be released to the next processing step.
Because of the fast moving product during granulation, short measurement cycles are needed. The latest Diode Array Detectors can take spectra in only a few milliseconds, allowing the customer to take chemical images of very small quantities of material or, by averaging these spectra over time, to adjust the measured volume of product to what is normally used in offline measurements. Other configurations are possible but speed of measurement is traded-off against the gain in resolution.
More accurate modelling thanks to the possibility to clean the probe prior to taking a reference measurement for modelling.
Enhanced reliability thanks to the automation of the system. The LightHouse Probe™ – DAD will perform a health check prior to usage to guarantee a correct measurement during process. This health check can also run online during production to ensure correct endpoint determination.

Suggested Configuration

For initial test work or for mobile test equipment, a manual probe is suggested while automated wash and CIP probes are designed for production.

For single pot processing including drying, a CIP probe is advised combined with a complete integration to change models between granulation and drying regime.

The LightHouse Probe™ fits on a standard 2” port, standard adaptor or weld-in ports can be provided. It is available as manual probe, automated wash probe and automated CIP probe.

Case Study

Genzyme reduces probe fouling and improves NIR data using the Lighthouse Probe™.

Genzyme, one of the world’s leading biotechnology companies, was looking for a PAT solution to control the high shear granulation of a development product by measuring a critical product attribute, rather than relying purely on time based processing or impeller current loading. The company used an optimized Lighthouse Probe™ to get representative NIR data of a granulation process. Read the article to learn how the data was then correlated to moisture content, bulk/tapped density and particle size of the final product.

Lighthouse Probe™ - NDC

Efficient Moisture measurement in fluidized bed dryers

Online Process Monitoring

“Plug and play”, no model development needed
No window fouling thanks to patented in process window cleaning
Reduced variability between drying batches and reduced waste
Suitable for all water based drying processes, solvent based processes on request
Accurate moisture measurement to better than ±0.25%.

Main Benefits

Low Cost of Ownership:
no need for model development. The Online LOD sensor uses NDC’s proprietary measurement algorithm, based on 20 years experience. Calibration requirements are limited to adjustment of the outputs slope and intercept, which can be done by the customer’s operators.
no need to wait for laboratory results. The finished batch can be released to the next processing step immediately when the drying step is finished.
Window fouling does not mean end of measurement. The probe can be manually or automatically retracted through a scraper seal to remove the deposits. Automated probes can even wash their windows on the machine without stopping or endangering the on-going drying process.
Improved Batch-to-Batch Consistency. Using the Online LOD sensor for endpoint determination will give more consistency between batches in moisture content of dried granules, enabling optimisation of product quality prior to the tablet press and eliminating the risk of over-/under-drying.
The Online LOD sensor is delivered with a filter wheel suited for moisture measurement. Dedicated filter wheels for solvent supplied on request.
The Online LOD sensor is delivered ready to measure the moisture content of a pharmaceutical powder within a range of 1% to 20% with a projected accuracy of ±0.25% subject to calibration verification and suitable compendial method.

Suggested Configuration

The Online LOD sensor is a LightHouse Probe™ equipped with an NDC PF710e gauge.

For initial test work or for mobile test equipment: manual probe
For integrated systems and if the probe is meant to stop the drying: automated CIP probe with additional soft- and hardware package.
For organic solvents, dedicated filter wheels can be provided per solvent

The probe can be mounted by welding a port into the vessel or alternatively by replacing a window with a specific adaptor.

The LightHouse Probe™ is available as manual probe, automated wash probe and automated CIP probe.

Process Analytical Technology

Lighthouse Probe™ - online measurement