Hydroxypropyl methylcellulose acetate succinate: potential drug-excipient incompatibility.
The stability of hydroxypropyl methylcellulose acetate succinate (HPMC-AS) and its potential incompatibility with active pharmaceutical ingredients (API) carrying hydroxyl group(s) were investigated in this research. HPMC-AS may undergo hydrolysis under harsh processing conditions with the generation of succinic acid and acetic acid, which can form ester bond(s) with the hydroxyl group(s) in API. In this case, the hot-melt extrusion (HME) product prepared from HPMC-AS and our model compound (compound A) was tested after heating at 140 degrees C up to 5 h. The succinate esters of compound A and its epimer were found in the product, suggesting potential drug-excipient incompatibility during formulation development. In addition, dyphylline was also tested with HPMC-AS and the potential incompatibility was further confirmed.
Dong
Zedong
Z
Pharmaceutical and Analytical Research and Development, Hoffmann-La Roche, Inc., 340 Kingsland Street, Nutley, New Jersey 07110, USA. zedong_dong@yahoo.com
Choi
Duk Soon
DS