Physical Stability Studies of Miscible Amorphous Solid Dispersions

ABSTRACTPhysical stability of 12 amorphous solid dispersions was evaluated over 9–22 months under ambient conditions using X-ray powder diffraction. The nine dispersions initially characterized as miscible drug-polymer systems all remained X-ray amorphous for the duration of their respective studies. In contrast, the three phase-separated systems all crystallized in 1–2 months, while the pure amorphous active pharmaceutical ingredients used in this study all crystallized within a few days, under the conditions of this study. Changes in the local order of dispersions that included polyvinylpyrrolidone were observed and appeared to correlate to periods of higher relative humidity (RH), reverting back to the original local order as the RH decreased. Phase-separation in the miscible dispersions as a result of ambient RH conditions did not appear to take place. Finally, formation of pores (voids) was observed through small-angle X-ray powder diffraction during crystallization of one model drug (felodipine). © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4005–4012, 2010