Preformulation Designed to Enable Discovery and Assess Developability

Michael   J.   Hageman

doi:10.2174/138620710790596781

Abstract

Physicochemical properties of drug molecules impact many aspects of both in vivo and in vitro behavior. Poor physicochemical properties can often create a significant impediment to establishing reliable SAR, establishing proof of principle type studies using in vivo models, and eventually leading to added performance variability and costs throughout the development life cycle; in the worst case scenario, even preventing execution of the desired development plan. Understanding the fundamental physicochemical properties provides the basis to dissect and deconvolute experimental observations in such a way that modification or mitigation of poor molecular properties can be impacted at the design phase, insuring design and selection of a molecule which has a high probability of making it through the arduous development cycle. This review will discuss the key physicochemical properties and how they can be assessed and how they are implicated in both discovery enablement and in final product developability of the selected candidate.

Keywords: Preformulation, solubility, stability, high throughput screening, lipophilicity, pharmacokinetics, absorption, formulation, solubilization