title: 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.
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08901, USA. preetanshu.pandey@bms.com
authors.forename: Preetanshu
authors.initials: P
authors.lastname: Pandey
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Sinko
authors.forename: Dilbir S
authors.initials: DS
authors.lastname: Bindra
authors.forename: Rhye
authors.initials: R
authors.lastname: Hamey
authors.forename: Shruti
authors.initials: S
authors.lastname: Gour
authors.forename: Chandra
authors.initials: C
authors.lastname: Vema-Varapu
mesh_terms: D003102:Colloids; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D013607:Tablets; D013997:Time Factors; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D003102:Colloids; D005079:Excipients; D013607:Tablets; D014810:Vitamin E; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; C014225:tocophersolan