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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. This article explains how the data was then correlated to moisture content, bulk/tapped density and particle size of the final product.
The reason for choosing a Lighthouse Probe™ was to expose as much product to the detector as possible. This was an important consideration for a high shear granulation process where changes in the process can happen quickly. Furthermore the scanning technology used in the spectrometer was FT-NIR, which has a relatively slow scan speed when compared to diode array based spectrometers.
Also the article describes how probe fouling was overcome, by using the probe in a high shear wet granulation process. The system is capable of being upgraded to a full GMP system for installation in production.
Genzyme was in phase three of the clinical trials of a new drug. The API had a small particle size, and associated poor flow properties. This presented Genzyne with a challenge when forming the dosage for patient administration. To improve the flow characteristics the API was to be formed into granules with other excipient materials by a high shear wet granulation process.
Genzyme chose to use the Lighthouse Probe™ from GEA Pharma Systems to monitor a high shear granulation process and to measure and quantify critical granule attributes. These measurements enabled the company to monitor the formation of the granules during the process to achieve an optimal granule size distribution.
The experiment used an FT-NIR spectrometer. This technology, whilst having high resolution and low signal-to-noise ratio for spectra, has a relatively slow scanning speed, compared to monochromatic-based spectrometers, such as diode array. Therefore, for the spectrometer to receive as much information as possible on what is occurring during the granulation process, a sample interface with a large window that would not suffer from fouling was required.
Genzyme were looking for a PAT solution which would enable control of the high shear granulation step for a development product by measuring of a product attribute, rather than relying purely on time based processing or impeller current loading.
The Lighthouse Probe™ showed that it is well suited to monitoring a high shear wet granulation process when used as the sample interface with a NIR spectrometer. It minimises the potential for probe fouling based on the 360° window and allows for the maximum absorbance of light from the spectrometer, with which to provide a signal for correlation.
The Lighthouse Probe™ produced satisfactory initial models against key granule attributes such as water content, particle size and bulk tapped density.
This study proved the feasibility of Lighthouse Probe™ technology for monitoring and eventual control of a high shear wet granulation process.
All business enquiries to:
Tomas Vermeire - Lighthouse Probe™ Product Manager
GEA Pharma Systems
Tel: +32 3 350 1258
Call +32 3 350 1293