A Direct Compression Formulation Refinement Algorithm

This algorithm captures some of the most common improvements that may be desired or required to modify the starting formulation. The algorithm is most likely to be used for medium dose APIs (10 to 50mg dose) or high dose APIs (above 50mg). 



To use the algorithm locate the diamond that describes the property that requires improvement and follow the “N” arrow to suggested solutions. For example, if the compression mix does not flow adequately then suggested improvements are to include fumed silica (Aerosil 200) at a level of 0.1 to 0.3% and/or to increase the particle size of the API (in the case of a medium or high dose API) provided that finely milled API is not needed for other reasons. As a rule of thumb a high dose API with D50 of 80 microns or above and a D10 of 10microns or above is likely to flow sufficiently well for Direct Compression.