Adjunct Professor and PharmaSolv Consulting, University of Montreal, Canada
Title: Chemistry and formulation-enabled drug delivery tools: Enabling discovery
Sophie Dorothee is a Adjunct Professor at University of Montreal and independent pharmaceutical consultant.
Formulation-enabled drug delivery tools such as nanomilling, amorphous solid dispersions, formation of micelles, and organic solubilizing vehicles are used to increase absorption and plasma exposures of poorly soluble drug substance molecules. Amorphization through spray-drying can lead to significant improvements in plasma levels providing the desired safety margins in preclinical species. Other tools, such as salts of the drug substance are often used to enhance absorption properties of potent drug candidates. Pro-active use of prodrugs earlier in the discovery space can provide significant benefits. Unlike the physical transformation through particle size reduction or amorphization, prodrugs are a chemistry-enabled drug delivery tool where the active parent is chemically modified to improve drug absorption. The prodrug is transformed in vivo into the active parent drug via enzymatic and/or chemical transformation and improve drug absorption, due to solubility or permeability enhancements. Improvements in metabolic stability leading to reduced dosing frequency and adverse events, can also be obtained through prodrugs. The advantages of pro-active use of formulation-enabled and prodrug (chemistry-enabled) drug delivery strategy early in Discovery will be highlighted using case studies. Using the right enabled technology at the right time and in the right wayis key to the selection of the right drug candidate for development.