(81d) Prediction of Tablet Dissolution from Real-Time Optical Coherence Tomography Data

The thickness and other quality aspects of pharmaceutical coatings are major impact factors for one of the most important quality attributes of a tablet, the dissolution profile. These quality attributes are conventionally determined by off-line measurement of weight or diameter gain. Optical Coherence Tomography (OCT) has attracted attention for at-line investigation and in-line monitoring of pharmaceutical film coatings [1]. This novel technology allows fast and non-destructive determination of thickness and other quality aspects of a representative number of coated tablets directly from the coating process. Implementation of OCT for an industrial scale pan coating process with capabilities for automated layer detection, classification (i.e. automated detection of tablets and layers), and thickness calculation in real time have been demonstrated previously [2].

This enables a systematic investigation of the link between coating quality attributes (e.g. coating thickness) measured in real-time and the target product quality attributes (e.g. dissolution). The goal of this study is to use the coating attributes measured in-line via OCT to develop a correlation model for the prediction of the expected dissolution profile, if a sample was taken at any point during the process. The talk will present the general workflow regarding how to develop a correlation model. The general workflow is applicable to obtain models for different formulations of tablets and pellets, which are coated via pan coating and fluidized bed coating, respectively. It will be demonstrated, how these models can be used to determine an ideal trajectory for the observed real-time values obtained via OCT, i.e. a golden batch trajectory, hence enhancing process robustness and enabling in-line quality control. The approach was developed and implemented in four representative use cases. The technology and method were transferred to different industrial sites such that their applicability across different industrial sites can be evaluated. The feasibility of this approach to contribute towards robust real-time release testing will be discussed.

[1] H. Lin, Z. Zhang, D. Markl et al., A Review of the Applications of OCT for Analysing Pharmaceutical Film Coatings. Appl. Sci. 2018; 8: 2700.

[2] S. Sacher, P. Wahl, M. Weißensteiner et al. Shedding Light on Coatings: Real-time Monitoring of Coating Quality at Industrial Scale. Int. J. Pharm. 566 (2019) 57–66.