(398s) Compaction Challenges With Solid Dosage Formulations Containing Vitamin E Tpgs

Compaction challenges with solid dosage formulations containing Vitamin E TPGS

Patrick D. Sinko¹, Preetanshu Pandey, Dilbir S. Bindra, Rhye Hamey

¹ Virginia Polytechnic Institute and State University, Materials Science and Engineering

² Bristol-Myers Squibb, Drug Product Science and Technology, New Brunswick, NJ USA

Vitamin E TPGS or TPGS (d-alpha tocopheryl polyethylene glycol 1000 succinate) is known to enhance the oral bioavailability of poorly water soluble drugs.^1,2 Given the high percentage of new chemical entities with low aqueous solubility it is may be desirable to incorporate TPGS in the formulation for such cases. This study assesses the processing challenges in incorporating TPGS into oral solid pharmaceutical dosage forms manufactured using a wet granulation process (high-shear and fluid bed). A solution of TPGS was prepared at 20% w/w concentration and added to the formulation as a binder. Tablets with up to 14% w/w TPGS were produced with no significant processing challenges when compressed at low tablet press speeds (dwell times ~ 100 ms).  However, at lower dwell times (<20 ms) that are typical of commercial-scale presses,  several tablet defects, such as tablet cracking, were observed during compaction.² A significant loss in compactability was observed as well. These compaction challenges were overcome through the intra-granular incorporation of Aeroperl® 300 (5-10% w/w), a granulated form of colloidal silicon dioxide. Interestingly, the addition of the same concentration of Aeroperl® 300 to the extra-granular portion did not provide the required compaction enhancement to the formulation. It was shown that the addition of intra-granular Aeroperl® 300 resulted in smaller granule particle size, higher granule porosity and higher compactability than the formulation without Aeroperl® 300.

References

1. Feiyan J, Tatavarti A. Tabletability assessment of conventional formulations containing Vitamin E tocopheryl polyethylene glycol succinate. Int J Pharm 2010;389:58-65.
2. Pandey P, Sinko PD, Bindra DS, Hamey R, Vema-Varapu C., Processing challenges with solid dosage formulations containing Vitamin E TPGS. Pharm Dev Tech 2013;18(1):296-304.