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

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Formulating Poorly Water Soluble Drugs

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 50))

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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 guidelines and (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 and detailed discussions of 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 that emphasizes the link between regulation and science.

This book chapter reflects the views of the authors and should not be construed to represent FDA’s views or policies.

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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 used 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)).

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Acknowledgments

The authors wish to thank Dr. Richard Lostritto, Dr. Christine Moore, and Dr. Stephen Moore for critically reviewing the manuscript and insightful discussions during the preparation of this book chapter for the first edition and Dr. Ramesh Raghavachari for the valuable comments during the revision of this book chapter for the third edition.

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Authors and Affiliations

  1. Silver Spring, MD, USA

    Zedong Dong & Hasmukh Patel

Authors
  1. Zedong Dong
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  2. Hasmukh Patel
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Editor information

Editors and Affiliations

  1. Division of Pharmaceutics, The University of Texas at Austin, Austin, TX, USA

    Robert O. Williams III

  2. Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA

    Daniel A. Davis Jr.

  3. DisperSol Technologies, LLC, Georgetown, TX, USA

    Dave A. Miller

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Dong, Z., Patel, H. (2022). Scientific and Regulatory Considerations for Development and Commercialization of Poorly Water-Soluble Drugs. In: Williams III, R.O., Davis Jr., D.A., Miller, D.A. (eds) Formulating Poorly Water Soluble Drugs. AAPS Advances in the Pharmaceutical Sciences Series, vol 50. Springer, Cham. https://doi.org/10.1007/978-3-030-88719-3_14

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