Revolutionizing White Coatings: A Titanium-Free Approach

INTRODUCTION

Titanium dioxide (TiO₂) has long been regarded as the most effective whitening agent for achieving a perfectly white tablet coating. However, concerns about its potential toxicity have sparked debate. Despite testing numerous alternatives, an efficient substitute remains elusive, even with increased coating weight and extended processing times.

The traditional sugar-coating process, which dates back to the mid-18th century, is labor-intensive and requires specialized equipment and skilled personnel. Leveraging insights into the optimal conditions for polyol crystallization, a novel coating process has been developed. Using xylitol as a base, this innovative approach simplifies and accelerates the hard-coating process, transforming it into a near-continuous crystallization cycle. Remarkably, this new process is compatible with existing equipment and operates at the same speed as film coating techniques.
Unlike film coating, hard coating is thicker and features a crystalline structure, offering a different pathway to achieving whiteness. This opens the door to exploring new substitutes for TiO₂, such as magnesium stearate, which shows promise as an alternative whitening agent.

OBJECTIVES

The aim of this study was to compare the whiteness of xylitol coatings containing varying ratios of magnesium stearate with a standard coating formulated using titanium dioxide, a well-established whitening agent. Additionally, the study sought to determine the magnesium stearate concentration required to achieve a comparable level of whiteness.

MATERIALS AND METHODS

Materials

XYLISORB® 300 xylitol, Roquette Magnesium Stearate (MgSt), LYCOAT® RS 720 modified pea starch from Roquette Frères (Lestrem, France).
Titanium dioxide from Kronos.

Methods

Mannitol tablets (400 mg, 130 N hardness) were coated with a red-colored, ready-to-use blend, ReadiLYCOAT® hydroxypropyl pea starch-based film coating system.

A mixture of xylitol, modified pea starch, and either magnesium stearate or titanium dioxide powders was prepared by blending in a DIOSNA high-shear granulator for 5 minutes (impeller speed: 250 rpm; chopper speed: 1800 rpm). The coating suspension was then formulated in water at room temperature with a dry substance concentration of 60%.

Due to xylitol's high cooling effect, the suspension temperature initially dropped to 2°C. It was subsequently mixed for 1 hour to allow the temperature to rise naturally to ambient conditions. Tablets were coated up to 30% weight gain using standard film coating equipment with samples collected at regular intervals.

The whiteness index (WI) was measured using a Konica Minolta CM-5 spectrocolorimeter under the following conditions: Reflectance mode; Standard illuminant: D65; Viewing angle:10°; Disc aperture:8mm; UV:100%.

RESULTS

Initially, a red film coating was applied to the tablets to achieve a deep color, allowing for an effective evaluation and quantification of the coverage provided by the second white coating.

One titanium dioxide (TiO₂) ratio and three magnesium stearate (MgSt) ratios were tested (Table 1).

Table 1. Composition of the different white coating solutions.

All polyol coatings (TiO₂ and MgSt) were performed with the same process parameters (Table 2).

Table 2. Coating parameters for all trials

Applying the parameters of the newly developed quasi-continuous polyol coating process, the coating was completed in 105 to 115 min. Neither titanium dioxide (TiO₂) nor magnesium stearate (MgSt) affected the coating process or the physical properties of the coated tablets, aside from differences in color and surface texture. Tablets coated with MgSt exhibited a very smooth surface, while those coated with TiO₂ had a rougher texture.
The reference coating for whiteness was achieved with 1% TiO₂, a commonly used concentration. Visual inspection and whiteness measurements confirmed the effectiveness of TiO₂ at this ratio. In contrast, higher ratios of MgSt were required to achieve comparable whiteness. A noticeable white covering on the initially red tablets began at a 4% MgSt ratio.
Three ratios were tested: 4%, 6% and 8% MgSt. The visual appearance of the tablets revealed a direct correlation between the MgSt ratio, and the level of whiteness achieved. Increasing the MgSt ratio produced a whiter color for the same coating layer thickness. For instance, 30% coating with 4% MgSt resulted in approximately the same whiteness as 15% coating with 8% MgSt (Figure 1).

Figure 1. Aspect of coated tablet at increasing coating weight gain for the tested formulations

Whiteness index (WI) was measured on all samples (Figure 2). WI and pictures gave the same outcomes: to reach the same covering power and whiteness than 1% TiO₂, MgSt must be incorporated at 6% minimum, while incorporating 8% MgSt enabled to reach the same whiteness with a lower coating deposition.

The thickness of the layer for a 30% coated tablet is about 350 – 400 µm. Consequently, the xylitol coating increased the hardness of the tablets (about 165 N versus 130 N initially) and the coated tablets are not friable at all.

CONCLUSION

Magnesium stearate (MgSt) in xylitol coatings enables the production of white tablets on colored cores. While MgSt is less effective than TiO₂, requiring approximately five times the content, a shift from film coating to crystallization coating accommodates this increase. The whiteness achieved is proportional to the MgSt content: for example, 15% coating with 8% MgSt matches the whiteness of 30% coating with 4% MgSt.

Additionally, MgSt eliminates the need for a smoothing step by directly producing a smooth surface, offering a practical advantage.

REFERENCES

1. Lefèvre, P., Haeusler, O., François, C., Croquet, S., Fast Tablet Coating with Xylitol, Poster, 4th European Conference on Pharmaceutics, 20-21 March 2023, Marseille, France.

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