Applied Drug Development Core Curriculum - Course Description

Who Should Attend

Scientists and technical managers working in pre-formulation at the drug discovery interface responsible for lead optimization and candidate selection. Attendees should include MS/PhD graduates new to the discipline and BS level scientists with significant experience in pre-formulation. Additional disciplines that would benefit from attendance include pharmaceutics/formulations scientists and managers interested in gaining better understanding of pre-formulation issues and discovery scientists desiring to increase their understanding of physical/chemical characterization principles. Individuals who have previously completed the CMC track of Applied Drug Development: Pre-Clinical and Drug Development Design Strategies would likely be well suited to attend this short course.

Goals & Objectives

This course covers practical aspects of pharmaceutical development at the early stage of drug discovery leading to candidate selection. The learner will become familiar with strategies and techniques pertaining to pre-formulation experiments conducted during lead optimization and selection. Specifically, the course is devoted to (1) those critical physicochemical properties of candidate molecules that are evaluated in order to assess their "developability" and (2) the formulation approaches used in discovery support to enable animal efficacy, PK and toxicological studies. Each day of the course focuses on one or more major topics: solubility, partition coefficients, solubilization, formulating poorly soluble compounds, oral bioavailability concepts, salt and crystal form searching and characterization, and chemical stability evaluation for solution and solid state. These key aspects of early pharmaceutical development will be integrated into a framework for candidate selection. This course is divided into morning sessions that are didactic in nature, covering background and experimental design aspects for each of the topics, illustrated by literature examples. The afternoon sessions are "case driven" in which attendees will learn how to analyze and interpret pre-formulation data through case examples. All data will be provided in spreadsheet format and analyzed at a computer in an instructor-led manner. Upon completion of the program, the learner will be able to:

1. Conduct solubility experiments with an ability to analyze pH-solubility data for pKa, intrinsic solubility and salt solubility product constants
2. Understand the basis for calculated solubility approaches and calculate solubility and pH-solubility profiles using a predominant method based on the "General Solubility Equation"
3. Design partition coefficient experiments to analyze pH-distribution data for partition coefficients inclusive of ion-pairing
4. Understand the basis for calculated partition coefficient approaches with an illustration of one such computer program (ACD/logP)
5. Apply major solubilization strategies for parenteral delivery, and for enhancing oral bioavailability of poorly soluble drugs for early preclinical evaluation, inclusive of practical limitations in pH, levels of organic solvents, oils, cyclodextrins and surfactants that can be dosed to animals and humans
6. Analyze solubilization data for key parameters such as solubilization power than enable optimization of formulations with minimal experimental data
7. Understand oral bioavailability concepts in the context of the biopharmaceutics classification system (BCS) and distinctions between dissolution rate, solubility and permeability limited absorption
8. Assess the relevance of solid state form and characteristics on prediction and measurement of physicochemical properties.
9. Apply solid state analysis techniques and crystallization concepts to salt and crystal form screening and selection.
10. Analyze solution and solid state stability data for candidate selection using principles of chemical kinetics
11. Design pH-rate and solid state stability protocols and perform appropriate experiments for early developability assessment and candidate selection
12. Analyze pH-rate and other stability data for catalytic constants and estimation of retest period and shelf life
13. Integrate all of the preformulation data into a composite profile to assess the developability of a candidate drug, identifying low and high risk features in the decision processApply solid state analysis techniques and crystallization concepts to salt and crystal form screening and selection.