Is there a correlation between the glass forming ability of a drug and its supersaturation propensity?

The use of an enabling formulation technique, such as amorphization of a poorly water-soluble crystalline drug, can result in supersaturation with respect to the crystalline form of the drug and thus potentially in a higher degree of absorption after oral administration. The ease with which such drugs can be amorphized is known as their glass forming ability (GFA). In this study, a potential correlation between GFA and supersaturation propensity is investigated. The GFA of 23 different drugs was determined by melt quenching or milling the crystalline drugs to obtain their respective amorphous forms. The inherent propensity of the drug to supersaturate, i.e. the maximal apparent degree of supersaturation (aDS), and the time until precipitation at a given aDS were determined. Supersaturation was induced via a solvent shift method where the drug was initially dissolved in dimethyl sulfoxide and then added to a biorelevant medium (fasted state simulated intestinal fluid).The study showed that drugs which are good glass formers also have the potential to supersaturate to a high degree (high maximal aDS) whereas drugs that are modest glass formers supersaturate only to a low degree. This correlation was confirmed by principal component analysis, which also indicated that melt enthalpy inversely correlated with both GFA and maximal aDS. However, no correlation between GFA of a drug and the time until precipitation at a given aDS was found.