Characterization of the coating and tablet core roughness by means of 3D optical coherence tomography

Abstract

This study demonstrates the use of optical coherence tomography (OCT) to simultaneously characterize the roughness of the tablet core and coating of pharmaceutical tablets. OCT is a high resolution non-destructive and contactless imaging methodology to characterize structural properties of solid dosage forms. Besides measuring the coating thickness, it also facilitates the analysis of the tablet core and coating roughness. An automated data evaluation algorithm extracts information about coating thickness, as well as tablet core and coating roughness. Samples removed periodically from a pan coating process were investigated, on the basis of thickness and profile maps of the tablet core and coating computed from about 480,000 depth measurements (i.e., 3D data) per sample. This data enables the calculation of the root mean square deviation, the skewness and the kurtosis of the assessed profiles. Analyzing these roughness parameters revealed that, for the given coating formulation, small valleys in the tablet core are filled with coating, whereas coarse features of the tablet core are still visible on the final film-coated tablet. Moreover, the impact of the tablet core roughness on the coating thickness is analyzed by correlating the tablet core profile and the coating thickness map. The presented measurement method and processing could be in the future transferred to in-line OCT measurements, to investigate core and coating roughness during the production of film-coated tablets.

Characterization of Pharmaceutical Tablets by X-ray Tomography

“…The pore size can vary between nm to m length scale, and with lab-based X-ray microtomography set-ups the resolution can be restricted up to a m. Hence, destructive techniques such as SEM or atomic force microscopy (AFM) need to be used to evaluate the smaller pores. Nevertheless, porosity can also be measured by non-microscopy methods without spatial resolution such as by He pycnometry or mercury porosimetry [ 247 ]. The porosity value links the macroscopic mechanical strength of the whole tablet, density variation can provide information on the local mechanical strength.…”

At-line validation of optical coherence tomography as in-line/at-line coating thickness measurement method

“…OCT measurements were performed using two different OCT systems. To acquire full volume information, an in-house 3D OCT prototype as described in (Markl et al, 2018) was used. Fully automated 1D OCT measurements were carried out via a commercial pharma OCT system (OSeeT Pharma 1D, Phyllon, Austria) equipped with exchangeable perforated rotating drums with an outer diameter of 200 mm.…”

“…Based on these data, a statistical evaluation of the readings can be performed. The 1D-OCT system evaluates the complete variation of a contiguous portion of the cross sections in the scanned area and calculates the coating thickness and its variation, as well the optical homogeneity of the layer and the surface roughness like presented by Markl et al (Markl et al, 2018).…”

“…In the years after, several research groups, including our own, have demonstrated that OCT is a very promising technology for non-destructive monitoring of pharmaceutical film coating processes (Lin et al, 2018) for tablets (Koller et al, 2011;Lin et al, 2015;Markl et al, 2015aMarkl et al, , 2014 and pellets (Li et al, 2014;Markl et al, 2015b). The literature indicates that OCT can provide information about critical material attributes, such as coating thickness, inner structure and homogeneity (intra-and inter-coating variability) of pharmaceutical coatings applied to tablets (Dong et al, 2017;Lin et al, 2017;Markl et al, 2018) and pellets (Li et al, 2014;Wolfgang et al, 2019). As a direct measurement technique, OCT does not require the development and maintenance of chemometric models for data interpretation, as is typically the case for near-infrared (Möltgen et al, 2013;Wahl et al, 2019) or Raman spectroscopy (Barimani and Kleinebudde, 2017;Müller et al, 2010).…”

A Review of the Applications of OCT for Analysing Pharmaceutical Film Coatings

“…The in-house OCT system was pumped by a Ti:sapphire femtosecond laser and achieved a lateral resolution of approximately 5 µm. The sub-surface imaging capability of OCT was exploited recently in [33], where the surface roughness parameters (root mean square deviation, the skewness and the kurtosis) for both the tablet cores and coatings were extracted automatically for coated tablets that were removed periodically from a pan-coating process. The measurements were able to show accurate coating variations across tablets' surfaces away from the edges.…”