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Discovering and Developing Molecules with Optimal Drug-Like Properties pp 209–240Cite as

Strategies and Methods for Drug Candidate Phase Optimization in Discovery Space

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Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 15))

Abstract

Identification of an optimal crystalline phase of a preclinical drug candidate plays a critical role in drug development, impacting bioavailability, solubility, stability, and physicochemical properties. Historically, drug candidate phase optimization was delayed until the development stage. More recently, however, these efforts have been moved earlier during the discovery stage. As such, an early understanding of a drug candidate’s phase behavior can clarify development liabilities and allow for more rapid development. This chapter begins with a rational for early phase optimization and describes critical attributes of an optimal development phase that impact scale-up and formulation design and performance. As detailed discussion on methods of phase screening, preparation and characterization is presented along with a brief section on preclinical formulation as it pertains to the selected solid state phase.

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Authors and Affiliations

  1. Formulation Sciences, Merck Research Laboratories, Merck & Co., 556 Morris Avenue, S7-E2-2679, Summit, NJ, 07901, USA

    Michael McNevin

  2. Discovery Pharmaceutical Sciences, Merck & Co., West Point, PA, USA

    John Higgins

Authors
  1. Michael McNevin
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  2. John Higgins
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Correspondence to Michael McNevin .

Editor information

Editors and Affiliations

  1. Pharmaceutical Sciences & Clinical Supply, Merck & Co, Inc., West Point, Pennsylvania, USA

    Allen C Templeton

  2. Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana, USA

    Stephen R. Byrn

  3. Discovery Pharmaceutics, Bristol-Myers Squibb, Wallingford, Connecticut, USA

    Roy J Haskell

  4. Department of Medicinal Chemistry, University of Kansas School of Pharmacy, Lawrence, Kansas, USA

    Thomas E. Prisinzano

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© 2015 American Association of Pharmaceutical Scientists

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McNevin, M., Higgins, J. (2015). Strategies and Methods for Drug Candidate Phase Optimization in Discovery Space. In: Templeton, A., Byrn, S., Haskell, R., Prisinzano, T. (eds) Discovering and Developing Molecules with Optimal Drug-Like Properties. AAPS Advances in the Pharmaceutical Sciences Series, vol 15. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1399-2_7

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