By Christopher W. Cunningham
Much focus in modern pharmaceutical development is on translational science, which is the idea that scientists and clinicians must work together to bring a drug candidate “from bench to bedside.” In other words, there is great need to find ways to bridge the large time gap between drug discovery and first-in-human clinical trials. One crucial juncture where drug candidates often fail is in preclinical development. A recent review on the subject by Guru Betageri of Western University of Health Sciences highlights the fact that attrition during the preclinical development phase in the drug development pipeline occurs due to lack of efficacy and issues associated with absorption, distribution, metabolism, elimination, and toxicity (ADME/Tox). Consequently, application of preformulation modeling in this juncture engages translational science by optimizing the results of drug discovery and development to fulfill the needs of preclinical and clinical assessment.
The formulation of a drug can impact its route and frequency of administration, its ADME and safety profiles, and its shelf life. The preformulation development and characterization of the physicochemical properties of a drug candidate provide the basis for the selection of suitable preclinical or clinical formulations. Properties such as molecular weight, pKa, log D7, solubility, and particle size can affect drug absorption and bioperformance. However, most of these properties are commonly experimentally measured to determine a formulation strategy, which requires a significant amount of time and resource investment. Accurate prediction of these properties would preclude the need for experimental assessment. A thorough understanding of the physicochemical properties can then accelerate formulation development, optimize bioperformance, and reduce timelines and risks associated with a drug candidate’s development. In silico approaches have the promise for guiding and enabling rapid formulation selection at an early stage.
To learn more about this timely topic, register for the AAPS webinar In Silico Tools in Preformulation and Formulation Development to be held on Thursday, May 8. This webinar, presented by Dr. Pierre Daublain and Dr. Dennis Leung of Merck, will summarize efforts made around the prediction of physicochemical properties of molecules and modeling of the absorption and bioperformance of drug candidates, and will describe how this information can be used to reduce the risks present in drug development.