Determination of the structural relaxation at the surface of amorphous solid dispersion using inverse gas chromatography

Amorphous dispersions provide an excellent way of increasing dissolution rates of poorly soluble drugs, but there may be concerns about stability. One way of assessing the stability of amorphous is the study of relaxation. In this study the relaxation at the surface of amorphous solid dispersions (SDs) was evaluated using inverse gas chromatography (IGC). A SD containing 70% indometacin and 30% PVP K30 was prepared by melt-quenching. The SD was put into the IGC and heated to 17°C below Tg for aging, during which time decane was injected repeatedly. The retention volume of decane decreased with aging time, indicating that the sample relaxed at the surface. During this storage no crystallization was observed by PXRD and DSC. Therefore, it is obvious that the change in this retention volume is due to the structural relaxation of the amorphous SD. The data of retention volume showed a good fit on a Kohlraush-Williams-Watts (KWW) equation and the indicator of the relaxation, τβ, was estimated. It was much lower than that of bulk relaxation estimated by DSC. Therefore, it can be concluded that the structural relaxation at the surface happens faster than that of the bulk. The potential significance of these findings is discussed. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2133-2139, 2009