(218d) Effects of the Solid Co-Solvent on the Melting Point Depression of Organic Substances

Orally disintegrating tablets (ODTs) are oral formulations having improved disintegration in the oral cavity that can be taken without water. It is possible to be applied to patients with fluid restriction and deglutition disorder. Recently, tabletting technology which uses high pressure carbon dioxide (CO₂) to induce a glass transition temperature depression of constituent polymers to crosslink the tablet particles was developed. By means of the technology, it is possible to increases the hardness with short time and mild temperature conditions. However, processing in high pressure is disadvantageous in terms of processing costs and safety. Therefore, we focused on the effects of solid co-solvent on the polymer to lower the processing pressure.

In this study, mechanism of the melting point depression due to the addition of the solid co-solvent was investigated. Ethyl cellulose (EC) and vanillin (VAN) was chosen as crosslinking polymer and solid co-solvent, respectively. EC/VAN physical mixtures of various mixing ratio were prepared by grinding in a mortar and successive sieving to obtain particles of less than 500 μm. Melting point of the EC/VAN physical mixtures under various pressures were measured visually, while that at the ambient pressure was determined by a DSC. Changes of intermolecular interactions before and after the pressure treatment were investigated by the FT-IR measurements.

At the ambient condition, the glass transition point of the EC became undetectable with the increase in the VAN content. Presumably, EC was dissolved in the melt of VAN. In all compositions, the melting point of VAN was observed at temperatures lower than that of the pure substance. With the addition of 5 wt% VAN, melting point of EC changed from 120 ^oC to 70 ^oC.

Melting point depression by pressure was observed for all samples including pure EC and VAN. With the increase in the VAN concentration, melting point depression became 5 ^oC (pure EC) to 40 ^oC (EC 20 wt%, VAN 80 wt%).  Visual observation of the melting revealed that the melting at atmospheric pressure occurs unevenly, and spots of liquid like points were observed in the field of view though, the melting occurred uniformly under pressure. This fact suggest the different mechanism of melting at ambient and at under pressure of CO₂.

From the results of IR measurement, peak shift was observed around 3300 cm^-1before and after the pressure treatment. It was found that the peak was shifted to about 10 cm^-1lower wave numbers. Which suggests the increase of the intermolecular hydrogen bonds by the pressure treatment.

In this study, co-solvent effects of VAN were clarified. These information is useful for the establishment of the new formulation processes.