Roll compaction granulation of a controlled-release matrix tablet formulation containing HPMC: Effect of process scale-up on robustness of tablets, tablet stability and predicted in vivo performance

A theophylline controlled release formulation was dry granulated using a laboratory-scale roller compactor. Roll pressure, screw speed, and roll speed were optimized and used to determine the direct scale-up equipment parameters. The tablet formulation then was scaled up to pilot scale and full production-scale roller compaction equipment. Direct scale-up involved the use of linear roll speed and compaction force per linear inch of roll width, Dry granulations were evaluated at several equipment variable settings established during the direct scale-up stage. Granulations and tablets prepared from the granulations were tested for physical properties and drug dissolution. Similarity in drug-release characteristics was determined by using f 2 metric analysis. Accelerated and ambient stability tests were performed on prepared tablets. Stability testing showed no major changes in tablet physical properties and drug release.