Principal Scientist AbbVie North Chicago, Illinois
Weak basic compounds demonstrate pH-dependent solubility with high aqueous solubility in acidic pH, but precipitation is observed in the intestine. Reports demonstrate prediction methods for oral absorption of poorly soluble weak base compounds using physiologically based biopharmaceutics model & in vitro experiments. In this study, we provide a modeling framework to assess the influence of precipitation on the oral absorption of weak base compounds using GastroPlus® and gPROMS FormulatedProducts® (gFP). We utilize multiple model compounds, then demonstrate how the precipitation model can be employed for biopharmaceutics risk assessment through oral absorption simulation using GastroPlus® and gFP. The incorporation of solubility & precipitation data into the model resulted in an accurate prediction of plasma profiles. This framework can help biopharmaceutics and formulations scientists to evaluate the risk of in vivo precipitation impacting drug product performance in early-stage development with limited amount of substance.
Learning Objectives:
Perform oral absorption modeling using in physicochemical properties, in vitro and clinical data, GastroPlus, and gPROMS FormulatedProducts®.
Assess Modeling Frameworks in Biopharmaceutics: Describe the use of software tools such as GastroPlus® and gPROMS FormulatedProducts® (gFP) for modeling the impact of dissolution and precipitation influence on drug product performance in early-stage development
Evaluate Risk in Drug Product Development:
Identify how the described modeling framework can be utilized by biopharmaceutics and formulation scientists to assess the risk of in vivo precipitation affecting drug product performance during early-stage development
