(742f) 3D Raman Spectroscopy – a Method for Mapping Ingredient Distribution throughout a Tablet Volume

Blending of powders can often result in agglomeration when one or more raw materials in a blend are cohesive, hydrophilic or have the tendency of acquiring electrostatic charges. Agglomeration often leads to failure modes in pharmaceutical tablets, particularly â??low doseâ? formulation tablets where the active pharmaceutical ingredient (API) is present in small amounts. When powders agglomerate, the uniformity of the final tablet is adversely affected, leading to variation in the tablet potency and dissolution profiles, which are usually undesirable. New technology enables the quantitative examination of the microstructure within tablets to determine the extent of agglomeration and to assess its effects on product performance. This can be useful as a means for understanding how the process causes agglomeration. If process parameters can be correlated to the tablet microstructure, this knowledge can assist in designing tablets of desirable quality thereby reducing product failure drastically.

Raman imaging is a powerful tool for studying tablet structure. It has higher chemical specificity than NIR and is also less affected by physical characteristics of the sample. The main disadvantage of Raman, its low quantum yield, requiring long integration times, is vanishing quickly, due to vast advances made recently in laser and detector technology. This is causing a significant renewed interest in using chemical mapping to examine the microstructure of pharmaceutical tablets.

This talk will focus on the use of a new Raman imaging platform, the mPAT system from H₂Optx, which is equipped with a 10x10 micron 2D spatial resolution along with the ability to shave layers off a tablet for depth analysis. This level of spatial resolution enables the user to extract detailed structural data that reveals the relationships between process, product structure, and product performance. This technique has the ability to do a quantitative content determination within a sample and, combining this for each pixel, generate 3D maps w.r.t. the individual constituents.

Tablets manufactured from traditional batch processing methods and continuous manufacturing methods were examined, including tablets made via Direct Compaction (DC), Wet Granulation (WG) and Roller Compaction (RC). Tablets using several formulations for each of the three methods were made with various levels of induced agglomeration and were analyzed using the mPAT system. The effects of the different processing conditions on agglomeration were characterized and their effect on tablet microstructure and dissolution were quantified. These observations will be discussed in this presentation.