Thursday, November 8, 2007 - 2:10 PM
565e

A New Hypromellose Excipient for Direct Compression Controlled Release

Karl Jacob1, Kacee Ender2, Tim Cabelka2, Dan Denomme2, and Dave Wallick2. (1) The Dow Chemical Company, 1319 Bldg, Midland, MI 48667, (2) Water Soluble Polymers R&D, The Dow Chemical Company, Larkin Lab, Midland, MI 48674

A common issue with controlled release direct compression excipients is their poor flowability. The goal of this project was to develop a new hypromellose excipient for direct compression (DC) controlled release formulations and to evaluate the performance of the new direct compression hypromellose in a direct compression tabletting process by comparing it to a standard METHOCEL(TM) K4M Premium controlled release grade in the same application. By appropriate application of particle engineering techniques, a better flowing excipient was prepared with improved flow as measured by reduced mean time to avalanche in an Aeroflow tester. In addition, the new excipient (in a metoprolol tartrate formulation) flowed freely through the tablet press hopper without the application of any external vibration. The variation in tablet weight was reduced from 31 mg to 4 mg (target tablet weight of 400 mg) with the improved excipient. The dissolution profiles of the new DC grade excipient and the standard controlled release grade nearly overlay (62-63% release after 5 hours) indicating comparable controlled release. The new DC hypromellose excipient improved the flowability of the directly compressed metoprolol tartrate formulation resulting in reduced tablet-to-tablet variability, while maintaining sufficient controlled drug release performance and tablet hardness.