Predicted Amorphous Solubility and Dissolution Rate Advantages Following Moisture Sorption: Case Studies of Indomethacin and Felodipine

Publication date: Available online 15 November 2018Source: International Journal of PharmaceuticsAuthor(s): Peter J. Skrdla, Philip D. Floyd, Philip C. Dell'OrcoAbstractWater 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 ...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research