(565e) A New Hypromellose Excipient for Direct Compression Controlled Release

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.