(336f) Linking Process, Product and Performance By Raman Imaging Analysis

Linking process, product and performance by Raman Imaging analysis

We employ Raman imaging to assess the spatial distribution of the components of a pharmaceutical tablet and its impact on performance measures such as in vitro dissolution and mechanical strength. We focus on tablets containing amorphous solid dispersion powders produced by spray drying and we vary the degree of heterogeneity by altering process parameters during sieving and blending steps.

Tablets containing Amorphous Solid Dispersions (ASDs) of poorly water soluble active pharmaceutical ingredients (APIs) in hydrophilic polymeric matrices are a commonly used strategy to increase the solubility and dissolution rate of oral-dosage forms [1]. Furthermore, many of the constituents of the amorphous dispersion/tablet are functional excipients selected to further enhance the bioavailability of the API [2].

Raman Imaging is a versatile analytical tool to provide chemical and spatially resolved information on dosage forms. Mapping the chemical composition throughout a section of a tablet provides a quantitative measure of the heterogeneity of each of the components within that section as shown in Figure 1. Additionally, it allows the detection of clusters which may arise from agglomerates not broken down during the blending step.

Figure 1: Raman imaging of the centre section of a pharmaceutical tablet indicating the spatial distribution of one of the components.

Herein a case-study is presented for a model drug where the same ASDs spray dried powder is formulated into a tablet with different process parameters following a design of experiments (DoE). In the DoE we vary the sieve mesh size and blending shear rates, known to have impact in individual component distribution within the tablet. Advanced analytical characterization by Raman imaging will be employed to evaluate tablet homogeneity. The influence of those parameters on the tablet tensile strength, friability, disintegration time and dissolution will also be studied, allowing an integration between process and product performance.

[1] Jermain, S. V., Brough, C., & Williams, R. O. / Amorphous solid dispersions and nanocrystal technologies for poorly water-soluble drug delivery – An update. International Journal of Pharmaceutics, 535 (1–2) (2018) 379–392

[2] S. Poozesh et al. / Understanding the process-product-performance interplay of spray dried drug-polymer systems through complete structural and chemical characterization of single spray dried particles. Powder Technology 320 (2017) 685–695