Solubilization of Poorly Water-Soluble Drugs: Theory and Applications

Abstract

This dissertation is based on the theory and applications of the most commonly used solubilization techniques: pH adjustment, cosolvency, micellization, complexation, and the combinations of pH adjustment with one of the other techniques.Chapter 1 provides an overview for the methods which are available to formulate a poorly water-soluble drug based on its administration route.Chapter 2 applies these commonly used techniques to solubilize two structurally related anticancer drugs. The efficiency of each technique is compared for both drugs side by side. It is observed that each technique is more efficient on the drug which has less polarity. However, the achievable final drug concentration in a formulation depends not only on the efficiency of the applied technique, but also on the drug's water solubility.Chapter 3 emphasizes the overall effectiveness of each technique on drugs which have different physicochemical properties. Solubilization profiles for the above techniques are generated for twelve compounds, eight of which are ionizable and studied under both unionized and ionized conditions. This chapter illustrates that the efficiency of the cosolvency, micellization, and complexation on both unionized and ionized drug species can be predicted from their polarities. Thus, the solubility of an ionizable drug can be estimated by using a given solubilizing excipient at any pH to meet the dose requirement.Chapter 4 studies the effect of cosolvent on complex stability. A series of alcohols were used to illustrate the effect of cosolvent size and polarity on the solubilization of a compound. It is proposed that a ternary drug-ligand-cosolvent complex is formed in these combined systemsThis dissertation provides guidance for the selection of a solubilization technique for a compound based on the physicochemical properties and the dose requirement.