Processing challenges with solid dosage formulations containing vitamin E TPGS

Abstract

The objective of this study is to investigate processing challenges associated with the incorporation of Vitamin E TPGS (d-α tocopheryl polyethylene glycol 1000 succinate) into solid pharmaceutical dosage forms. For this work, a wet granulation process (high-shear and fluid bed) was used and Vitamin E TPGS was added as part of the binder solution during granulation. It was shown that Vitamin E TPGS can be incorporated into a prototype formulation at 10% w/w concentration without any significant processing challenges. However, the resulting granulations could only be compressed successfully at low tablet press speeds (dwell time ~100 ms). When compressed at low dwell times (<20 ms) representative of commercial tablet manufacturing, a significant loss in compactability was observed. In addition, several other tablet defects were observed. It was shown that intragranular incorporation of Aeroperl® 300, a granulated form of colloidal silicon dioxide, was able to overcome these compaction problems. The formulation consisting of Aeroperl® 300 showed significantly lower granule particle size, higher granule porosity and higher compactability as compared to the formulation without Aeroperl® 300.