Starting process for Direct Compression

A key success factor in Direct Compression, especially for low dose drugs, is achieving good content uniformity. This in turn requires a good mixing plan to disperse agglomerates of finely milled active ingredient and to distribute the API through the compression mix.

Our recommendation is therefore to prepare an initial premix of the API with some of the Direct Compression excipient and then to subject the premix to a high shear step to disperse agglomerates. In the laboratory this step is readily achieved by passing the premix through a 500 micron sieve. Other processes include for example blending the premix using a blender fitted with an intensifier bar. To avoid unnecessary damage to the Direct Compression excipient we recommend the premix includes only a portion of that excipient, for example 20%.



The improvement in tablet homogeneity can be seen in the plots below, where a 5mg dose of API has been used. A simple mixing plan without a step to disperse agglomerates gave a tablet with 154% label strength and an overall tablet RSD of 8.1%. When a sieving step was included all tablets were within 98% to 105% label strength and the RSD was reduced to 1.6%.

Red arrows indicate single tablet assays more than 15% from the target.