Before a prospective active pharmaceutical ingredient (API) or drug can be successfully placed into a dosage form for clinical trials and licensure, we must have a clear understanding of its properties and behavior in the environment in which it will be stored and upon exposure to the body. Toward this end, experiments are carried out to discover the API’s fundamental chemical properties such as solubility in different solvents; dissociation constant (pKa); salt formation; partition or distribution coefficient (log P or log D); pH solubility profile and dissolution kinetics; permeability; susceptibility to oxidation, temperature, humidity, and light; and its stability in solid and solution state. Drug-excipient and drug-drug compatibility studies are also conducted to investigate potential interactions that could impact the API’s stability and/or efficacy. Further, transporter and metabolizing enzyme studies are performed to investigate what may happen to the drug in vivo.
A thorough preformulation assessment provides the basis for developing a robust dosage form that can maintain integrity during manufacturing, shelf life, and in vivo delivery. Sufficient time spent on a comprehensive preformulation assessment provides cost savings in the long run by reducing challenges during formulation development.