Flow-through cell method and IVIVR for poorly soluble drugs

Abstract

The percentage of poorly soluble compounds in drug discovery and development increases steadily. A variety of possibilities exists for increasing solubility and bioavailability; among them is the formation of salts. For the characterization of poorly soluble active pharmaceutical ingredients (API), it is necessary to develop appropriate analytical methods to determine relevant physicochemical properties. One important physicochemical parameter is the dissolution rate. As the flow-through cell (FTC) offers various advantages, such as operating with pH gradients and in sink conditions or applying unlimited amount of media, the FTC is particularly suitable for poorly soluble compounds. When developing an FTC method it is important to consider the physiological circumstances. By choosing the appropriate conditions for media, volume, flow rate, and so forth, it is possible to predict in vivo behavior. The focus of this work was to develop a small-scale FTC method for poorly soluble compounds designed for determining dissolution kinetics in the early development phase, where only limited amount of drug is available. The predictive power of the presented system could be demonstrated by an in vitro-in vivo relationship (IVIVR) study.