(693g) Half Tablet Methodology: Investigating the Relationship between Dissolution Behavior and Raman Chemical Imaging

There are known knowledge gaps in the current pharmaceutical manufacturing processes, particularly regarding the relationship between processing conditions, and resulting particle size and spatial distribution of drugs in solid dose products. These three aspects can be linked through a common feature of understanding the physical and chemical microstructure of a tablet. A better understanding of tablet microstructure has the potential to unveil the relationship between process parameters and performance attributes, mainly dissolution. 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 spatial resolution and chemical specificity than NIR and is also less affected by physical characteristics of the sample.

This study focuses on using a commercial three-dimensional (3D) Raman Imaging system (H2Optx), as an off-line measurement system, to find a relation between chemical information obtained from Raman Imaging and API dissolution. Till now, extensive structural studies have not been conducted to study this relationship using Raman Imaging.

In this work, Ibuprofen (D50: 70 µm) is jet milled to two more particle size ranges (D₅₀: 28 and 11 µm) following by mixing with Fast Flo Lactose (filler) and Magnesium stearate (lubricant) a V-Blender with two levels (high and low) of shear. The six conditions were expected to have contrasting dissolution behaviors and Raman Chemical Images. Post blending, tablets were manufactured using an MCC Presster (a rotary tablet press simulator). An FT-NIR Transmittance based PLS regression model predicted the API content in each of the marked tablets. The ‘deviated’ and ‘normal’ tablets from each of the experimental conditions were cut in half with minimal powder loss. One-half (from each of the tablets) was used for dissolution test while the other half was used for 3D Raman Imaging. Statistical comparison of 3D Raman Images and dissolution profiles revealed the relationship of the chemical microstructure to the dissolution process. The overall methodology is described in the figure below: