{Reference Type}: Comparative Study
{Title}: Predicted amorphous solubility and dissolution rate advantages following moisture sorption: Case studies of indomethacin and felodipine.
{Author}: Skrdla PJ;Floyd PD;Dell'Orco PC;
{Journal}: Int J Pharm
{Volume}: 555
{Issue}: 0
{Year}: Jan 2019 30
{Factor}: 6.51
{DOI}: 10.1016/j.ijpharm.2018.11.042
{Abstract}: Water is often readily absorbed by amorphous compounds, lowering their glass transition temperature (Tg) and facilitating their recrystallization (via nucleation-and-growth). At the same time, the increase in moisture content translates to a decrease in both the thermodynamic solubility and intrinsic dissolution rate, as compared to the corresponding dry (pure) amorphous phase, e.g. see [Murdande SB, Pikal MJ, Shanker RM, Bogner RH. 2010. Solubility advantage of amorphous pharmaceuticals: I. A thermodynamic analysis. J Pharm Sci 99:1254-1264.]. In the case of pure indomethacin and felodipine, the solubility advantage of each amorphous phase over its crystalline counterpart were previously determined to be 7.6 and 4.7, respectively, using a new methodology together with basic calorimetric data taken from the literature. Herein, we demonstrate that, theoretically, following the uptake of just ∼0.5% w/w water, the solubility ratios decrease to 6.9 and 4.5, in the same order. Moreover, as the predicted intrinsic dissolution rate (based on the Noyes-Whitney equation) is directly proportional to the solubility advantage of a given amorphous-crystalline pair, it decreases proportionately upon moisture uptake. Applying the methodology presented herein, one can directly predict the extent of Tg-lowering observed at any moisture content, for a given amorphous phase. Knowing that value, it is possible to estimate the relative decrease in the solubility and/or intrinsic dissolution rate of the plasticized phase compared to the pure glass, and vice-versa.