Improving Oral Bioavailability of Poorly-Permeable Peptides
Li Li
Principal Scientist, Merck Research Laboratories
Oral delivery is a desirable route of administration for peptide therapeutics but is hindered by poor absorption and molecular instability in the gastrointestinal tract. Through the use of preclinical models and strategic formulation design using permeation enhancers, improvements in bioavailability and efficacy at low doses can be realized in the clinic. The presentation will highlight the formulation development strategy for oral peptide (PCSK9i), which centered on the use of permeation enhancers (PE) to improve absorption. Due to the lack of confidence in the pre-clinical models predicting PE performance, multiple formulations were developed in order to study key factors (e.g., PE type, PE amount, colocation of PE/peptide, ect) potentially impacting peptide absorption in humans. The formulation complexity and limited API call for disciplined formulation and analytical development approach to allow formulation screening in rapid succession with human PK as input to drive formulation decision.
Li Li is a Principal Scientist at Merck Research Labs. She received Ph.D. in Chemistry from Drexel University. She joined Pharmaceutical Sciences organization in 2001 and is responsible for developing predictive in vitro methodology and designing stability studies for over 20 Merck drug candidates ranging from pre-clinical to Phase III. More recently, she co-led the early development team for Oral PCSK9i, a potentially transformative therapy for patients with a high risk for a CV event.