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Nanosizing: “End-to-End” Formulation Strategy for Poorly Water-Soluble Molecules

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Discovering and Developing Molecules with Optimal Drug-Like Properties

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

Abstract

The number of poorly water-soluble compounds in pharmaceutical research and development pipelines has steadily increased over the years. These compounds have historically been difficult to develop requiring high concentrations of solvents/co-solvents and exhibiting poor pharmacokinetic properties. In response to this unmet need, a variety of niche technologies have been explored and developed. This chapter reviews one of the more versatile “end-to-end” formulation approaches for poorly soluble compounds, i.e., nanosizing or nanonization. The approach is broadly applicable for parenteral and non-parenteral dosage forms and has been commercially validated with the launch of products such as Rapamune®, Emend®, TriCor® 145, Triglide®, Megace ES®, Invega® Sustenna®, Abraxane®, and Juvedical®.

The terms nanosuspension, nanocrystalline drug particles, nanoparticles, and nanosized formulation are used interchangeably throughout this chapter when referring to a dosage form wherein the active pharmaceutical ingredient (API) has a mean particle size less than one micron.

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Acknowledgements

Special acknowledgement is given to Gary G. Liversidge, Ph.D. for his many contributions to NanoCrystal technology and its applications and for his invaluable encouragement and input in writing this chapter. In addition, I thank Tarek Zeidan, Ph.D., Chris Hencken, Ph.D., Jules Remenar, Ph.D., Fidelma Callahan, Eva Stroymowski, and Amy Trevvett for their critical reviews, to all past colleagues of Nanosystems LLC, and Elan Drug Technologies, and to the current management of Alkermes for their support.

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  1. Pharmaceutical Research and Development, Alkermes, INC., 852 Winter Street, Waltham, MA, USA

    Elaine Merisko-Liversidge

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  1. Elaine Merisko-Liversidge
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Correspondence to Elaine Merisko-Liversidge .

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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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Merisko-Liversidge, E. (2015). Nanosizing: “End-to-End” Formulation Strategy for Poorly Water-Soluble Molecules. 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_13

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