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Formulating Poorly Water Soluble Drugs pp 603–629Cite as

Scientific and Regulatory Considerations for Development and Commercialization of Poorly Water-Soluble Drugs

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Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 3))

Abstract

This chapter focuses on the Chemistry, Manufacturing, and Controls (CMC) from the scientific and regulatory perspective of the development of poorly water-soluble drugs to provide insights into regulatory filing from Investigational New Drug Application (IND) to New Drug Application (NDA) submission. The chapter includes two primary sections to cover the two regulatory stages for CMC module of filing, IND and NDA. The IND section of the chapter includes the following contents: (1) brief description of general filing requirements as outlined in the Code of Federal Regulations (CFR) and relevant guidances; (2) discussion of potential regulatory issues for developing poorly water-soluble drugs using various pharmaceutical technologies in the IND stage, i.e., solid-form selection, particle-size reduction, lipid formulation, and amorphous solid dispersion. The NDA section of the chapter includes the following: (1) general regulatory filing requirements of an NDA application; (2) potential regulatory issues associated with poorly water-soluble drugs; detailed discussions are carried out on topics including solid-form selection of the drug substance, drug product development using novel pharmaceutical technologies, development of control strategies, etc.; (3) case studies of marketed drug products of poorly water-soluble drugs in various dosage forms; this part uses the public information of the approved products as examples to support the discussions as outlined in part (2); and (4) brief discussion on the concept of Biopharmaceutics Classification System (BCS) in the development of poorly soluble drugs. The book chapter concludes with a brief summary which emphasizes on the link between regulation and science.

This book chapter was written by Zedong Dong and Hasmukh Patel in their private capacity. No official support or endorsement by the Food and Drug Administration is intended or should be inferred.

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Notes

  1. 1.

    Drug substance means an active ingredient that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or any function of the human body, but does not include intermediates use in the synthesis of such ingredient (21 CFR 314.3(b)).

  2. 2.

    Drug product means a finished dosage form, for example, tablet, capsule, or solution, that contains a drug substance, generally, but not necessarily, in association with one or more other ingredients (21 CFR 314.3(b)).

  3. 3.

    Active also refers to drug substance.

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Acknowledgement

The authors wish to thank Drs. Richard Lostritto, Christine Moore, and Stephen Moore for critically reviewing the manuscript and insightful discussions during the preparation of this book chapter.

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Authors and Affiliations

  1. Office of New Drug Quality Assessment, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA

    Zedong Dong & Hasmukh Patel

Authors
  1. Zedong Dong
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  2. Hasmukh Patel
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Correspondence to Zedong Dong .

Editor information

Editors and Affiliations

  1. , Division of Pharmacy, University of Texas at Austin, Mailstop A1920, Austin, 78712, USA

    Robert O. Williams III

  2. College of Pharmacy, Drug Dynamics Institute, University of Texas, Austin, 78712, Texas, USA

    Alan B. Watts

  3. , Pharmaceutical and Analytical R&D, Hoffmann-La Roche, Inc., Kingsland St 340, Nutley, 07110, USA

    Dave A. Miller

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© 2012 American Association of Pharmaceutical Scientists

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Dong, Z., Patel, H. (2012). Scientific and Regulatory Considerations for Development and Commercialization of Poorly Water-Soluble Drugs. In: Williams III, R., Watts, A., Miller, D. (eds) Formulating Poorly Water Soluble Drugs. AAPS Advances in the Pharmaceutical Sciences Series, vol 3. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1144-4_14

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