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Solubility Enhancement

Fig. 1. Overview of important features of amorphous solid dispersions
Fig. 1. Overview of important features of amorphous solid dispersions

Many important substances including new drugs, agricultural chemicals and nutraceuticals are often very insoluble in water. This can make them very hard to formulate and deliver and may even prevent new drugs from being clinically efficacious. Several strategies have emerged to improve aqueous solubility and drug delivery including salt formation, amorphous solid dispersions, cocrystals, complexation, lipid formulations and combinations thereof. The Taylor group is actively involved in research topics pertinent to solubility enhancement and how the different enhancement methods compare with one another. The group has considerable expertise with amorphous formulations, and amorphous solid dispersions are of particular interest. Research in this area encompasses all aspects of the design, production and characterization of amorphous solid dispersions as summarized in Fig. 1. We have studied drug-polymer miscibility which is essential to ensure that the drug doesn't crystallize during storage of the formulation. The role of polymers in inhibiting crystallization from the solid formulation is also a topic of fundamental and practical importance. Much of our research in this area has focused on understanding the role of drug-polymer intermolecular interactions on the miscibility and crystallization kinetics of the drug.

Maximum attainable solution concentration

For extremely poorly water soluble compounds, an important question that has to be addressed is "how much can the solubility be increased by using a solubility enhancing formulation?". This is a difficult question to address. For solubilization strategies that lead to supersaturation, it is crucial to consider the phase behavior of the compound. Relevant phase transitions are crystallization of the drug and liquid liquid phase separation. If crystallization is rapid, then it may be very difficult to achieve sustained solubility enhancement. In this instance, it is important to determine if crystallization inhibitors can be added to the formulation to help prolong the supersaturation duration. For compounds that crystallize more slowly from water, if the solution is highly supersaturated, the spinodal decomposition point may be exceeded resulting in liquid-liquid phase separation (LLPS). The resulting disperse phase may appear solid-like or liquid-like depending on the glass transition temperature of the phase separated material. In this instance, the solution will remain supersaturated, despite containing a precipitate, and the supersaturation will persist until crystallization occurs. It is therefore important to understand the different types of precipitation phenomena that can occur from supersaturated solutions.

Solid State Stability

Maintaining the solid state stability of drug in a dosage form is extremely important to ensure product quality. Changes that can occur in dosage forms include conversion of a salt to the free form, polymorphic transformations, crystallization of amorphous solids, and deliquescence of highly soluble components. These changes can lead to variations in product performance such as reduced dissolution rates or increased tablet hardness. We are interested in detecting, characterizing and understanding factors that impact solid state phase transformations.