Raman Spectroscopy as a PAT-Tool for Film-Coating Processes: In-Line Predictions Using one PLS Model for Different Cores

Although Raman spectroscopy has been described as a potential process analytical technique for tablet coating, it has rarely been transferred from academic studies to commercial manufacturing applications. The reasons for this are probably not only the high level of process understanding and experience with multivariate data analysis required, but also the product-dependent elaborate model-building. Hence, this study represents a feasibility study to investigate, whether subtraction of core spectra is a suitable approach to generate versatile models for one specific coating that can be applied on a multitude of different tablet cores. Raman spectroscopy was used to predict the application of coatings on three different tablet cores using PLS regression. The obtained spectra were preprocessed, and differential spectra were calculated by subtraction of the core spectrum from each inline spectrum. Normalization ensured comparability between the spectral data of the different cores. It was shown that in general it is possible to build models for a specific coating suspension that can predict the application of this suspension on different cores. In the presence of a strong Raman marker (TiO2), promising results were obtained. Without the presence of a strong Raman marker this modeling approach is to be considered critical.

Continue reading here: Radtke, J.; Rehbaum, H.; Kleinebudde, P. Raman Spectroscopy as a PAT-Tool for Film-Coating Processes: In-Line Predictions Using one PLS Model for Different Cores. Pharmaceutics 2020, 12, 796.

Keywords: Raman spectroscopy; process analytical technology (PAT); coating; partial least squares; chemometrics

Materials and Methods

Tablet Cores

Coating suspensions were applied on three different biconvex tablet cores: acetylsalicylic acid (ASA) cores, diclofenac cores and placebo cores. ASA cores were produced via direct compression using a Korsch XL 200 tablet press (Korsch AG, Berlin, Germany). They consisted of 62.1% ASA, 6.9% corn starch, 30% microcrystalline cellulose (Vivapur® 102 J. Rettenmaier & Söhne GmbH + Co KG, Rosenberg, Germany) and 1% sodium stearyl fumarate (Pruv®, J. Rettenmaier & Söhne GmbH + Co KG, Germany). The cores had an average mass of 239.6 mg, a diameter of 8.0 mm, a 4.2-mm height and a 2.8-mm band height. Diclofenac cores were produced via direct compression in a Korsch XM 12 (Korsch AG, Germany), containing 12.5% diclofenac sodium, 36.5% alpha–lactose monohydrate (FlowLac® 100, Molkerei Meggle Wasserburg GmbH & Co. kG, Wasserburg am Inn, Germany), 50% microcrystalline cellulose (Sanaq 102, Pharmatrans-Sanaq AG, Allschwil, Switzerland) and 1% magnesium stearate (Parteck LUB MST, Merck KGaA, Darmstadt, Germany). These cores were produced with an average mass of 205.6 mg, a diameter of 8.0 mm, a tablet height of 4.02 mm and a 2.02-mm band height. Placebo cores were provided by L.B. Bohle Maschinen + Verfahren GmbH. They consisted of 99% dicalcium phosphate (DI-CAFOS® 150, Chemische Fabrik Budenheim KG, Budenheim, Germany) and 1% magnesium stearate. The placebo cores had an average mass of 252.4 mg, a diameter of 8.1 mm, a tablet height of 3.42-mm and a band height of 2.05 mm.

Coating Suspensions

Experiments were performed using two different coating suspensions. One suspension was an enteric coating, while the other was an immediate release coating. The first coating suspension was an enteric ready-to-use coating based on a copolymer of methacrylic acid and ethyl acrylate. The suspension contained 20% AquaPolish® (AP) P white 712.02 E (Biogrund GmbH, Hünstetten, Germany), 2% propylene glycol (Cesar & Lorentz GmbH, Hilden, Germany) and 78% demineralized water. AquaPolish® P white 712.02 E is a one-step film coating system containing acrylic acid copolymer and TiO2 in the anatase modification. The second coating suspension consisted of 15% AquaPolish® P white 014.117 (Biogrund GmbH, Hünstetten, Germany) and 85% demineralized water. AquaPolish® P white 014.177 is a TiO2-free white HPMC/HPC-based ready-to-use mixture. Calcium carbonate and dicalcium phosphate are contained as white pigments. Both coating suspensions were permanently stirred during the coating process.