MOISTURE CONTENT

MEASUREMENT

CASE STUDY This case study is based on a large research-focused health

care company with a long tradition in pharmaceutical production

and diagnostics.

The company was founded by people intricately involved in

spectroscopy and process analytical technologies, long before the

FDA published PAT guideline in 2004. The experts of the company

paved the path for PAT in different companies, overcoming different

process issues like window fouling, integration and system prices.

The two companies came together accelerating the implementation

of this advanced technology in the industry.

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THE CHALLENGE

DETERMINING THE MOISTURE CONTENT OF GRANULES IN A FLUID BED DRYER

In tablet production, a drying process is needed to ensure

moisture levels are reached after granulation. Granulation is

either done in a Fluidized bed or high shear granulator to

guarantee particle size uniformity and equal distribution of Ingredients. This process can cause significant delays in tablet

manufacturing with room for errors and potential product loss.

The challenge lies in accurately and consistently determining

the moisture content of granules in a fluid bed dryer, the most

common granulation process. The wrong drying conditions can

result in damaged particles, uneven product uniformity such as

distribution of APIs, and breakable tablets.

Wet granulation is typically done in batch process, requiring

the drying phase to standstill many times for offline analysis.

Alternatively, the process continues blindly based on an

operator’s experience. Both of these methods extend

production time and increase risk that granules are not at

optimum moisture content.

The best results come from Near-Infrared, NIR, reflectance

spectroscopy application for in-line, contact measurement of

moisture content in a fluidized bed.

The pictures to the left show typical window fouling: the first

demonstrates a heated probe tip in a high shear granulator

freshly installed. The second picture shows the location probe

in between sediments on a fluidized bed wall. The ingredients

dried on the lens and later required cleaning at the end of

granulation.

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THE CHALLENGE

WINDOW FOULING

When the US Food and Drug Administration launched the PAT Initiative in 2004, the company

investigated a number of in-process measurement systems. Almost without fail, the single most

common factor that interfered with the process and prevented operators from obtaining accurate data

was window fouling.

The Lighthouse Probe™ can be used to monitor chemical and pharmaceutical processes in real-time,

providing a clear view inside the production vessel, even in difficult conditions. Offering in-process

window cleaning and recalibration, the device is fully clean-in-place (CIP) compatible and available in

both manual and automated versions.

Offering standalone to fully integrated and multivariate functionality, the Lighthouse Probe™ optimizes

production by minimizing variation, reduces waste, provides valuable data, saves money and offers a

constantly clear view into the process vessel.

The graphs represent data from a 10 minute

granulation run on a high shear granulator. It is

clear from the graphs that the probe missed an

important part of the process due to window

fouling. This caused inaccurate readings of

moisture until the process was stopped, the

probe was cleaned and measurements could

resume.

The first graph emphasizes when the powder

sticks to the probe. The heat from the probe

window quickly dries the powder thus moisture Level decreases, demonstrating a trough in the graph. This creates a false moisture reading caused

by window fouling.

Thanks to the cleaning steps and calibration, the spectra used for modelling can be trusted not to

suffer from any bias caused by window fouling. This will generate a very accurate model.

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THE SOLUTION LIGHTHOUSE PROBE™

The quest for a better method ended with Lighthouse Probe™ moisture sensor

NIR measurements of moisture in-line and In-process recalibration at any time

in real-time

Eliminates inaccurate calibrations caused

In-process window cleaning at any time by window fouling

In-process control of window cleanliness at Full CIP of wash and housing seal

any time.

Always a clear view inside with The

Lighthouse Probe™

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AUTOMATIC CLEANING MECHANISM

Product sticking to the observation window is no

longer an obstacle with contact measurements.

As the sides and windows of a dryer become

fouled The Lighthouse ProbeTM can use its in-line

window scrape and/or wash functionality to keep a

clear view at all times. Calibration measurements

are also taken without the bias of window fowling

resulting in an accurate, automatic calibration.

Cleaning

The advantage of the window

cleaning capabilities in

combination with the easy

calibration method of the

moisture sensor makes this a

fast and very reliable tool for

online moisture determination.

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THE RESULTS

The test was done with a Glatt dryer and the Lighthouse Probe™ mounted on, in-line with

the sampling unit and the temperature sensor.

During the operation the probe was moved between measurement and calibration

positions to clean it’s windows just before taking a calibration reference. During the first

batch, 5 calibration points were recorded to establish the correlation with the offline

analysis method. This exercise yielded the calibration values needed to configure the

moisture meter.

Online Data Offline Data

Sample ID LOD RSD LOD1 LOD2 LOD3 Average St Dev

Sample 1 1,00 0,042 0,9 0,95 1,04 0,96 0,071

Sample 2 1,07 0,039 1,04 1,09 1,08 1,07 0,026

Sample 3 1,16 0,025 1,06 1,14 1,19 1,13 0,066

Sample 4 1,03 0,025 1,01 1,02 1 1,01 0,010

R² 0,97 RMSEP 0,026% LOD

The calibrated system was then used in 4 different batches and the performance was

checked by taking samples during the drying and comparing them with the online results.

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COMMERCIAL BENEFITS

The initial benefit comes from the reduction in product waste as line moisture

determination always involves the risk of batch failures. Each rejected batch is an

enormous financial investment and wastes resources. The use of the Lighthouse Probe™

eliminates this risk.

Longer term, the Lighthouse Probe™ enables monitoring the moisture content of the

granules more carefully thereby helping to produce granules that are easier to handle in

the following tableting process and produce a more clinically effective product. These

benefits are more difficult to calculate objectively but are potentially much greater.

The Lighthouse Probe™ is a practical solution to the problem of assessing moisture

content during the granulation process. It requires the company to take fewer

measurements, reduces costs and produces a more effective and consistent product.

For further information: sales@indusmation.com

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