(565c) 3D Raman Imaging: A Method to Study the Effects of Lubrication on the Microstructure of Tablets

3D Raman Imaging: A Method to Study the Effects of
Lubrication on the Microstructure of Tablets

Shashwat Gupta, Savitha Panikar, Fernando Muzzio

Rutgers- The State University of New Jersey

When it comes to pharmaceutical
tablets, there are known knowledge gaps in the
current manufacturing processes, particularly regarding the
relationship between material properties of ingredients, processing conditions,
and resulting tablet attributes. These three aspects can be linked through a
common feature of understanding the microstructure of a sample. A better understanding of tablet microstructure has the potential to
unlock the black box between process parameters and performance attributes.
Product structure understanding of this nature can aid in prediction of product
performance, process development as well as deviation investigations. Understanding the microstructure of a tablet requires knowing the
spatial distribution of the different ingredients and void space, which can be
enabled by Chemical Imaging (CI).

Raman imaging is a
powerful tool for studying tablet structure, with superior chemical specificity
than NIR and is also less affected by physical characteristics of the sample.

This study focuses on
using 3D Raman Imaging system (H2Optx), as an off-line measurement system, to
bridge this gap for tablets made using a Direct Compression (DC) continuous
line, for the lubrication process. For pharmaceutical operations, lubrication
is essential in order to reduce the friction between the surfaces of
manufacturing equipment and that of organic solids as well as to ensure the
continuation of an operation. The most common pharmaceutical lubricant used is
Magnesium Stearate (MgSt). Till now, extensive structural studies have not been
conducted to study the effects of lubricant(s) on tablet properties.

In this work, we
investigate the particle size distribution, spatial variability (Variograms) of
MgSt, using the 3D Raman Images. These parameters are then correlated with product
performance (tablet hardness and dissolution profile) as well as formulation
(amount of MgSt) and process parameters (Total exposure to shear and Residence
Time), with the help of Principle Component Analysis.

Variographic data
helped to quantify the distribution of MgSt in tablets of experimental
conditions. On the other hand, to discern the variability in the distribution
of MgSt within the layers of a tablet, we needed PCA score plots of the
variographic data obtained from the 3D Raman images. They revealed a stark
difference in the clustering of the layers for the tablets with different
process and formulation parameters.  The hardness of the tablets from the two
experimental conditions agree with the expected trend. A wider distribution of
MgSt resulted in tablets with a lower tablet hardness. However, there is not a
clear trend in the dissolution profile with respect to the distribution of
MgSt.

An example of a
comparison between 3D Raman Images of tablets elucidating the effect of total
exposure to shear is shown below:

                                                                        (a)

                                                                        (b)

Figure 1: 3D Raman
Images (a) Lower exposure to shear: MgSt, green – particles <50 microns, red
– particles from 50 to 250 microns and (b) Higher exposure to shear: MgSt,
green – particles <50 microns, red – particles from 50 to 250 microns

The future research
will involve studying how the distribution of MgSt changes in a tablet, as we
move ahead in a continuous line i.e. comparison between post blending and post
tableting samples. All the work will be used as a platform for an on-line
measurement system.