Amorphous solid dispersions (ASD) are a common formulation approach for orally delivered small molecule active pharmaceutical ingredients (APIs) whose oral bioavailability (BA) is limited by dissolution rate and/or solubility in the gastrointestinal tract. Some of the foremost reasons this method has become so prevalent are the large potential for gains in bioavailability, easily assessable and mature manufacturing platforms, and straightforward integration of the resultant dispersions into an oral solid dosage form. Given the amorphous form of the API has significantly higher free energy than its neutral crystal form, it will have a higher aqueous solubility, and therefore, a more rapid dissolution rate. For these reasons, it is fairly straightforward to formulate an ASD that has improved BA compared to its crystalline form. However, it can be challenging to formulate a shelf-stable ASD that maximizes absorption potential and at the same time optimizes attributes amenable for downstream processing into an oral solid dosage form.
