Content considerations for low dosage drug formulations processed by roller compaction

The roller compaction of low dosage drugs was evaluated using Pseudoephedrine HCl as a model drug. Roller compaction was done using a Fitzpatric Model L-83 Chilsonator. The active drug, Pseudoephedrine HCl coarse powder, was mixed with several diluents and diluent combinations. The effect of the diluent on granulate characteristics was evaluated. The diluents used included hydrous lactose, dibasic calcium phosphate, Avicel PH 101, 102, 105 and 200. The excipients were characterized in terms of their cohesiveness alone and in combination with other excipients. This was done using both angle of internal flow and angle of repose measurements. The compressibility and deformation characteristics were determined by the Heckel relationship. The diluents were evaluated either alone with the active or in combination with other diluents with the active. When the diluents were used alone, the active was distributed in a distinctive and reproducible manner throughout the granulation. There were differences in the behavior with each individual diluent. The combinations were found to have predictable outcomes based on the concentration of each diluent used. The parameters for the experiment were set by the statistical method of extreme vertices. The extremes were set based on the behavior of the individual diluents. Combinations of the diluents were prepared and the data provided suitable statistics that described the system. Using computer simulation, the diluent blends were manipulated to produce the ideal granulation. The data collected in this experiment allowed for the prediction and optimization of the granulation properties produced by roller compaction. Through the optimization, the best excipients for use in the preparation of the granulations of active ingredients can be determined. The method outlined here may be utilized for roller compaction evaluation for any combination of excipients. It may provide a standard evaluation method that could be applied prior to the final selection of excipients for roller compaction processes