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By Allen C. Templeton

Allen Templeton-finalDiscovering and developing molecules with optimal drug-like properties presents a number of notable challenges, yet it is key toward the long-term success of product development and value to patients. With most laboratories shifting away from the “shots on goal” strategy, there has been a renaissance in pharmaceutical sciences collaborating with discovery to design molecules optimized with drug-like properties from the outset. Challenges in the area include evaluating both new research techniques as well as strategy for implementation.

There has been a move toward predictive and high-throughput approaches to understand key properties such as solubility, stability, and bioperformance. Identifying and managing the risks around these parameters and others is paramount for translating a molecule into a stable, processable, and bioavailable drug product. The practical realities of performing physical pharmacy and biopharmaceutics research in the context of drug discovery with short timelines and low compound availability are examples of real issues faced in the field. Thus, being able to perform information-rich experiments with minute quantities of material is becoming increasingly relevant.

bioassay using liquid handler

Discovering, characterizing, and assessing risks on the solid state properties of advanced discovery and early development candidates has to be connected with solid state properties such as compound phase, salt form, and morphology. These, in turn, are linked to critical development parameters such as solubility and stability. Physiochemical properties form the scientific basis for formulation strategy and decision-making and form the basis of experimentation such as excipient compatibility, formulation screening, and materials assessment.

In essence, the goal of research in the area is to get the discovery scientist to pay proper attention to physiochemical properties during molecular design in discovery with the aim of producing more druggable molecules. At the same time, it has to be recognized that some targets are simply unamenable to low molecular weight, soluble, hydrophilic moieties, and this is where advanced formulation tactics can be deployed most successfully. Molecular optimization for difficult-to-drug targets can lead to molecules well-suited for an array of enabled formulation approaches to achieve desired bioperformance. Another interesting element is the link between patient and medical needs for the product and formulation design and optimization.

We’ve recently tried to cover much of these topics in the new book Discovering and Developing Molecules with Optimal Drug-Like Properties, which recently became available and debuted at the 2014 AAPS Annual Meeting in San Diego.

Allen C. Templeton is executive director of analytical sciences at Merck Research Laboratories and is responsible for the managing staff in the pursuit of scientific problem-solving for pharmaceutical product development utilizing measurement sciences.