FORMATION OF A PHYSICALLY STABLE AMORPHOUS DRUG COMPLEX

Abstract

ABSTRACT In this paper we explore the use of Neusilin, an inorganic magnesium aluminometasilicate, to stabilize the amorphous form of an acidic drug a neutral drug and two basic drugs. Both cryomilling and ball milling of the drug with Neusilin were found to produce the amorphous phase. However the ball milled material exhibited superior physical stability when compared to the cryomilled material at 40 oC/75% RH. 13C SSNMR investigation of the ball milled material revealed an acid-base reaction between the acidic drug and Neusilin. Optimal milling conditions and the kinetics of salt formation were also established. As bench-top milling is a lab scale process, a scalable process was developed to make the acidic drug/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 bench top 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 outperform tablets made from crystalline Sulindac. For the broad class of acidic drugs containing the carboxyl moiety, Neusilin or other similar silicates would be better choices to stabilize amorphous phase than organic polymers.