Manufacture and Performance Evaluation of a Stable Amorphous Complex of an Acidic Drug Molecule and Neusilin

In this paper, we explore the use of Neusilin, an inorganic magnesium aluminometasilicate, to stabilize the amorphous form of an acidic drug Sulindac. Both cryomilling and ball milling of the drug with Neusilin were found to produce the amorphous phase. However, the ball‐milled (BM) material exhibited superior physical stability when compared with the cryomilled material at 40°C/75% relative humidity. 13C solid‐state nuclear magnetic resonance investigation of the BM material revealed an acid-base reaction between Sulindac and Neusilin. Optimal milling conditions and the kinetics of salt formation were also established. As benchtop milling is a laboratory‐scale process, a scalable process was developed to make Sulindac-Neusilin amorphous drug complex using hot‐melt extrusion (HME). The dissolution properties of the resulting HME material was found to have been improved over the material made by benchtop milling while maintaining similar physical stability. The HME material was used to make tablets using a direct compression method. The HME tablets were found to have better dissolution properties than tablets made from crystalline Sulindac. For the broad class of acidic drugs containing the carboxyl moiety, inorganic silicates such as Neusilin would offer a better choice than organic polymers to stabilize the amorphous phase. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:3332-3344, 2011