Early‐Stage Formulation Considerations

Robert W. Lee1, Mark Mitchnick1

1 Particle Sciences, Inc., a Lubrizol LifeSciences Company, Pennsylvania, Bethlehem
Publication Name:  Current Protocols in Chemical Biology
Unit Number:   
DOI:  10.1002/cpch.32
Online Posting Date:  December, 2017
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When a drug candidate—i.e., a new chemical entity (NCE) or new molecular entity (NME)—is discovered, there is a requirement to identify a vehicle for in vitro and/or in vivo evaluation to assess the activity and/or toxicity of the compound (here we refer to the biologically active compound as the active pharmaceutical ingredient: API). Ideally, this vehicle will not impart any biological activity or any toxicity that would mask or confound the effects of the API. At this early stage in development, and given the high attrition rates of drug candidates in discovery, it does not make sense to fully characterize the API—speed and cost are generally the driving factors. This chapter provides guidance for the development of early‐stage test articles (i.e., drug products containing APIs intended to be used for the in vitro and/or in vivo evaluation) and not necessarily formulations that are intended to progress into clinical evaluation. © 2017 by John Wiley & Sons, Inc.

Keywords: drug discovery; new chemical entity; new molecular entity; preformulation; test article; vehicle

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Table of Contents

  • Introduction and Purpose
  • Preformulation and Analytical Characterization Considerations
  • Considering the Biopharmaceutical Classification System for Formulation Evaluation
  • Formulation Approach—Strategic
  • Formulation Approach—Tactical
  • Concluding Remarks
  • Literature Cited
  • Figures
  • Tables
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Literature Cited

Literature Cited
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  Ku, M. S. (2008). Use of the biopharmaceutical classification system in early drug development. The AAPS Journal, 10(1), 208–212. doi: 10.1208/s12248‐008‐9020‐0.
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  Lee, R. W., Shaw, J. M., McShane, J., Wood, R. W., & Shenoy, D. B. (2008). Particle size reduction. In R. Liu (Ed.), Water‐Insoluble Drug Formulations, (2nd ed., pp. 467–498). Boca Raton, FL: CRC Press.
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  Mitchnick, M., & Lee, R. W. (2012). Comments on biopharmaceutical classification system and formulation development. Life Science Connect, Guest Column, Retrieved from https://www.pharmaceuticalonline.com/doc/comment-biopharmaceutical-classification-formulation-development-0001.
  Waring, M. J., Arrowsmith, J., Leach, A. R., Leeson, P. D., Mandrell, S., Owen, R. M., … Weir, A. (2015). An Analysis of the attrition of drug candidates from four major pharmaceutical companies. Nature Reviews Drug Discovery, 14, 475–486. doi: 10.1038/nrd4609.
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