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By: Marshall Crew, Christopher Lipinski, Jasmine Musakhanian, and Mehran Yazdanian


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Late stage drug lipinski-102814-headshotpipelines in pharmaceutical companies continue to remain anemic in spite of the abundance of drug candidates coming out of discovery. This is in part attributed to the efforts of medicinal chemists to produce massive libraries of compounds with burgeoning molecular sizes, structural complexities, and very poor solubility characteristics for diverse biological targets. There is also a perceived (or real?) lack of formulation technologies to adequately address the druggability issues presented by the modern day development candidates.

Specifically, the following questions are worthy of consideration:

  • Which is the more cost and time effective approach to improving the rate of success in drug development? Investing in the upstream, in the drug discovery stage focusing on compounds with “optimal” druggability? Or downstream, focusing on novel drug delivery technologies?
  • Given the advances in drug delivery technologies, have the definitions of druggability changed over the past two decades?
  • Can the decades old boundaries set for druggability and developability be expanded beyond the Rule-of-5 to increase the number of molecules that reach the formulators’ bench?
  • Do medicinal chemists need to take an entirely different approach to traditional drug discovery?
  • Should drug discovery scientists (drug discovery science?) focus primarily on identifying and synthesizing the most potent, efficacious, and safe molecules and leave the delivery to formulation scientists?
  • Is investing more in formulation technologies to improve the drug solubility and permeability shortcomings a more cost- and time-effective strategy than redesigning molecules and introducing other unintentional challenges for development scientists?
  • Should druggability be defined by the oral route of administration? What about parenteral, transdermal, or other routes of administration? Why does the oral route trump all the other options?
  • When does discovery stop and formulation begin in the development process? Do they need to work in tandem? What are the benefits of having formulators involved early on in discovery?

Where to invest? The Drug or the Delivery System? is a tongue-in-cheek question chosen as the title of an upcoming Dialogue and Debate session at this year’s AAPS Annual Meeting and Exposition. The session will be on Thursday November 17, 10 am to noon. This session aims to address the questions listed above as well as informing and engaging a broader audience in a conversation on the decisions that are made from the design of a new chemical entity for a specific target in any therapeutic area in discovery to selection of optimal drug delivery systems to achieve the desired efficacious exposures in the clinic.

We hope that this debate will help narrow the divide between the upstream drug discovery and the downstream formulation technologies; create a much needed dialog between the two ends of the drug development spectrum; and ultimately carve a path for more successful and shorter drug development processes.

We invite you to join the session and add your comments and experience to the debate on where to invest in order to select and deliver the most efficacious and safe drug to the patients. If you’re unable to attend the session, we’d love to read your thoughts below in the comments section.

Marshall Crew, Ph.D. is vice-president of global PDS scientific excellence at Patheon. He has devoted his career to developing innovative technologies and approaches for the delivery of poorly soluble drugs.
Chris Lipinski, Ph.D., is a consultant and Scientific Advisor to Melior Discovery. He is a  renowned scientist whose publication of the “Rule of Five” in 1997 is a landmark paper in the medicinal chemistry literature.
Jasmine Musakhanian, is the Scientific & Marketing Director at the Pharmaceutical Division of Gattefossé Corporation.  She completed her studies at McGill University in Montreal with a bachelor’s in Food Science and a master’s in Protein Chemistry in 1986.
Mehran Yazdanian, Ph.D. is the senior director of pharmaceutics at Teva Branded Pharmaceutical Products R&D Inc. His area of expertise is in biopharmaceutical properties affecting oral absorption in drug candidate selection and product development.