(189x) Solubility Enhancement of Hydrophobic Drug Molecules Via Amorphous Solid Dispersions and Flash Nanoprecipitation

Authors: 
Caggiano, N. J., Princeton University
Prud'homme, R. K., Princeton University
Priestley, R. D., Princeton University
Hydrophobic small molecule drugs present unique obstacles for oral administration. Their physical properties, namely poor aqueous solubility and large oil/water partition coefficient, often result in poor in vivo bioavailability. It is estimated that 60-70% of pipeline drug candidates may be classified as BCS Class II compounds, which exhibit solubility-limited in vivo absorption. Thus, there is an opportunity to improve the bioavailability of such compounds by enhancing their aqueous solubility. One strategy for solubility enhancement involves generating and stabilizing the amorphous form of the drug molecule in drug-polymer systems. Lacking the long-range order present in the crystalline form, the amorphous material represents a higher energy state compared to the crystalline state. This greater free energy increases the thermodynamic driving force for dissolution, resulting in improved aqueous solubility. Our research investigates two platform technologies for producing amorphous drug-polymer systems: Amorphous Solid Dispersions (ASDs) and Flash NanoPrecipitation (FNP). Here, we illustrate our study of these two technologies to enhance the aqueous solubility of hydrophobic drug molecules. We show that the amorphous form of the drug can be obtained as a result of the fast dynamics of the spray drying and FNP processes and that the amorphous drug is further stabilized in the solid form by the chosen amphiphilic polymers. We present characterization of our materials and an assessment of release performance and supersaturation.