(T1130-03-20) Fast Tablet Hard Coating with Xylitol

Purpose: The hard coating process consists in covering a core with a adhering shell for organoleptic, friability reduction, moisture seal with a great galenic potential. Sugar and polyol coating are based on crystallization while hard coating process do not follow the basic physical conditions for crystallization. The high drying temperature in the coating pan hinders the aimed crystallization, favoring the re- dissolution of already formed crystals. Trials were done to better understand traditional hard coating process drawbacks to optimize process transforming it to a quasi-continuous crystallization cycle using xylitol as a coting excipient.

Methods: Materials: Xylitol Xylisorb® 300 from Roquette Freres (Lestrem, France);Titanium dioxide (grade 1171) from Kronos Titan GmbH (Leverkusen, Germany);Modified starch from Roquette Freres (Lestrem, France). All hard coating trials were done in regular film coating equipment using different batch sizes (from 1kg scale up to big quantities). For this example, we used:RAMA COTA, with a 19’’perforated pan; Spray gun: Schlick 970/7-1 S75 (nozzle diameter 0.8mm) Pump: Watson Marlow model 323, Head: 313 DW. The coating syrup was prepared out of a dry powder blend (see table 1). It is used as a 60% DS syrup, dissolved in water at room temperature. The hard coating runs via spraying the 60% DS syrup on the cores (quantities e.g. 5kg), targeting a coating level between 5% and 30% weight gain. The basic process conditions are: Pan speed:8 RPM; Inlet air temperature: 45°C;Tablet bed temperature: 30-35°C; Spray rate: 3.5 to 8.5 g/min/kg. The spray rate is usually low in the first process phase, to trigger the continuous xylitol crystallization process. After the stabilization of the process (typically after 5% weight gain), the spray rate increases up to 8.5g/min/kg. In some rare cases, a reduced coating rate during the end phase of the process assists for a better surface smoothing and finishing.

Results: The selected process conditions leverage some traditional obstacles to obtain a fast and complete crystallization: Lowering the bed temperature limits the xylitol solubility and also the viscosity of its saturated solutions (e.g. on the tablet surface during the coating process). This is particularly important for xylitol, having a significantly higher solubility /temperature dependence than saccharose (see figure 1). Targeting a lower but constant core bed temperature permits a faster crystallization, due to a higher mobility of the xylitol molecules. The xylitol crystallization enthalpy assists the water evaporation and permits a rapid weight gain without excessive heating. In consequence, it is possible to switch to a continuous crystallization state, permitting a very fast and homogenous weight gain. Anyhow, the tablet surface remains dry during the whole xylitol coating process. The tables 2 and 3 summarize the differences between the tradition hard coating process and the rationalized process. Applying coating levels up to 20% did not bridge tablet logos. (See figure 3 ) It is therefore possible to standardize/automatize the coating process, meeting pharmaceutical production standards. Adding a polymer gives the coating layer more mechanical resistance (e.g. Arabic gum or pregel starch), preventing edge chipping. The presence of titanium dioxide provides high opacifying properties (see figure 2). Typically, the coating level of about 15% could completely cover colored and/or inhomogeneous tablets. (See figure 2). The pigment quantity can be adapted to the formulation needs. Alternatively, it is possible to design white, but titanium dioxide free, recipes and colored versions.

Conclusion: A rational approach of the hard coating process permitted a new, quasi-continuous coating process. It requests only one coating cycle and is therefore much faster than the traditional hard coating. In addition, it runs in tradition film coating equipment und does not request supplementary equipment. It permits to obtain white or colored hard coatings, permitting also to preserve tablet logos (without bridging) up to a coating level of about 20%.

References: 1. WO2018234248A1, Sugar coating method and sugar coated solid forms with irregular shapes, December 2018

Figure 1. Solubility of xylitol and sugar at different temperatures

Figure 2: xylitol coated, initially red colored tablets.