Dissolution behavior of amorphous solid dispersions

Matthew J Jackson, Purdue University


Current drug discovery techniques tend to identify potential new drug entities with more complex structures which may pose significant formulation challenges. In particular, an increasingly large number of new drug compounds have extremely poor solubility in water, impacting the bioavailability of the drug. Solubility enhancement techniques, such as amorphous solid dispersions (ASDs), can be used in oral dosage forms to increase the apparent solubility of the drug in the gastrointestinal tract thus increasing the bioavailability of the drug. However, the drug solution generated from the dissolution of an ASD formulation is supersaturated. In other words, the solution concentration is higher than the crystalline solubility. These solutions are therefore thermodynamically unstable and can crystallize. Recent evidence suggests that some systems can undergo another phase transformation prior to crystallization, namely liquid-liquid phase separation (LLPS). LLPS creates a discrete drug-rich phase dispersed in the continuous aqueous drug-lean phase and is expected to impact the bioavailability of the drug though effects on diffusion and crystallization behavior. Currently there is a lack of understanding of the mechanisms underlying the complex phase behavior of these supersaturated solutions of poorly water soluble drugs, crucial to the formulation of amorphous solid dispersions. The work presented within this thesis is focused on developing the techniques necessary for studying complex phase behavior through the investigation of a model drug system. The relationship between amorphous solubility and supersaturation was examined and correlated to the dissolution of amorphous solid dispersions. The ability to predict, evaluate, measure, and understand supersaturated drug solutions and the associated phase transitions, specifically LLPS and crystallization, is critical to the formulation and overall effectiveness of ASDs.




Taylor, Purdue University.

Subject Area

Pharmacy sciences

Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server