Impact of solid state properties on developability assessment of drug candidates

Adv Drug Deliv Rev. 2004 Feb 23;56(3):321-34. doi: 10.1016/j.addr.2003.10.007.

Abstract

Solid state properties including polymorphism, solvate and salt formation can have a profound impact on two of the most important properties that are essential to the successful development of drug candidates: solubility and stability. To enable meaningful evaluations of drug candidates for their development risks, often referred to as developability, and provide input to the molecular design regarding the "drug-like" properties, one must take into account the impact of solid state properties on solubility and stability. This review examines the importance of solid state properties and their relationship to developability criteria. Phase appropriate characterization strategies and appropriate salt and crystal form screening and selection processes are discussed. These strategies and processes should balance the need for speed and throughput of modern discovery with the quality of data essential to the adequate developability assessment. Specific examples are given to illustrate the importance of understanding the solid state properties and their impact on developability.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Chemical Phenomena
  • Chemistry, Physical
  • Crystallization / methods
  • Drug Stability*
  • Humans
  • Molecular Conformation
  • Pharmaceutical Preparations / chemistry*
  • Salts / chemistry
  • Solubility
  • Solvents / chemistry
  • Technology, Pharmaceutical / methods*
  • Transition Temperature

Substances

  • Pharmaceutical Preparations
  • Salts
  • Solvents