Maximizing the solubility advantage of amorphous pharmaceutical systems

David E Alonzo, Purdue University

Abstract

Many pharmaceutical compounds are quite insoluble in their crystalline state. As a consequence, there is a significant amount of research interest in the area of solubility enhancement with the ultimate goal of increasing bioavailability. The ability of amorphous pharmaceuticals to the enhance solubility and bioavailability of active pharmaceutical ingredients has been well documented. However, these high energy solids and the supersaturated solutions they generate are inherently unstable. A lack of fundamental understanding of the key parameters required for effective stabilization is one reason these materials are not utilized more frequently. Instability can be interpreted very broadly when discussing amorphous solids, but the focus of this research is on the generation and stabilization of supersaturated solutions. In order for an amorphous solid to be effective at increasing bioavailability over its crystalline form, a supersaturated solution of the API must be present in the gastrointestinal tract for a biologically relevant timeframe. There are two requirements which must be met in order for this to occur. First, the amorphous solid must remain amorphous during dissolution long enough to generate the desired supersaturated solution. Second, there must not be substantial crystallization of this supersaturated solution prior to the drug being adequately absorbed into the body. Stabilization of both the amorphous solid and supersaturated solution can be achieved by incorporating polymers into the system. Some of the major factors that contribute to the performance of these systems include dissolution rate, degree of supersaturation, crystallization of the amorphous solid during dissolution and crystallization from the supersaturated solution. Therefore, understanding fundamentally how these factors relate to the performance of amorphous solids and the impact that polymers have on that performance is the objective of this thesis. Improving this understanding will enable formulations scientists in the pharmaceutical industry to effectively design amorphous formulations that will lead to predictable bioavailability enhancement.

Degree

Ph.D.

Advisors

Taylor, Purdue University.

Subject Area

Pharmacy sciences

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