Details:
Understanding the physicochemical properties of a compound such as solubility, stability, lipophilicity, ionizability and permeability is essential in drug discovery and development process. Frequently these parameters are not adequately addressed until unsatisfactory absorption has been found in the clinic, thus delaying or even stopping further development of a promising new drug candidate. In this workshop we will focus on solubility and permeability, the two important properties that are used to define Biopharmaceutics Classification System (BCS).

We will discuss how drug substance form selection and particle size characterization will affect the solubility and dissolution. In addition, biopharmaceutical assessments involving studies of solubility and permeability in biologically relevant system (in vitro and in vivo) such as oral bioavailability, PK variability and food effect will be included; both preclinical and clinical strategies will be covered.

The workshop will be beneficial to discovery, CMC, DMPK and pharmacology scientists who are involved with identifying small-molecule drug candidates and bringing them to early development stage.

Workshop Outline:

1.Introduction

• Overview BCS and intestinal drug absorption; Importance of physicochemical and biopharmaceutical characterizations in discovery and early development

1. Solubility and dissolution

• Solubility and dissolution determination
• The effect of forms and particle size on solubility and dissolution
• Relevance of in vitro dissolution tests to in vivo absorption properties

1. Permeability and In-vivo biopharmaceutics tools

• Permeability and in vitro/in vivo tools
• Preclinical models to predict food effect and pH dependent drug-drug interactions in human

1. Strategies to evaluate physicochemical and biopharmaceutical properties for candidate selection (1 hour)
2. Biopharmaceutics assessment in the clinic

• Oral bioavailability and PK variability
• Food effect
• DDI with pH modifying co-meds
• Predicting clinical outcome based on biopharmaceutics properties using modeling & simulation

1. The FDA Biopharmaceutics Classification Systems (BCS) Guidance (30 min) and regulatory perspectives