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Nonsink In Vitro Dissolution Testing of Amorphous Solid Dispersions

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Melt Extrusion

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 9))

Abstract

Solid dispersion technology has been used over the last three decades to improve the dissolution and oral absorption of poorly soluble compounds. While the characterization of dissolution performance of crystalline pharmaceutical systems has long been established, the dynamic nature of the amorphous dissolution processes requires the use of unique methodologies. The in vitro differentiation of the drug and drug-containing species of these systems is crucial to accomplishing the measurement of the critical-to-performance free drug concentrations as a function of time. This chapter describes the theoretical aspects of amorphous dissolution and recent examples applying free drug dissolution testing to the oral bioavailability assessment of solid dispersion formulations.

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Notes

  1. 1.

    Amorphous solid dispersion (ASD) is used to describe a homogenous dispersion of noncrystalline API and excipient(s) at molecular compositions. Similar systems are often described as solid dispersions, amorphous molecular dispersions, solid solutions, solid liquids, and others.

  2. 2.

    It is typically stated that between 40  and 70 % of new chemical entities under development in the pharmaceutical industry are insoluble (van de Waterbeemd and Gifford 2003 ; Benet and Wu 2006 ).

  3. 3.

    (a) Zelboraf (vemurafenib) CDER (2011), (b) Incivek (telaprevir) Bottorf et al. (2007) , (c) Intelence (etravirine) Pomerantz (2007) , (d) Kaletra (lopinavir and rotinavir) Rosenberg et al. (2008) , and (e) Cesamet (nabilone) Dong (2005) .

  4. 4.

    Center for Drug Evaluation and Research Application No. 202429, Clinical Pharmacology and Biopharmaceutics Review(s), www.accessdata.fda.gov.

  5. 5.

    http://www.pharmacopeia.cn/v29240/usp29nf24s0_c711.html.

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Acknowledgments

The author would like to thank the following individuals and organizations: Marshall Crew, Dan Smithey, and James Fennewald at Agere Pharmaceuticals, Inc. for contributions to the in vitro drug speciation dissolution studies, and Shaukat Ali and Nigel Langley at BASF for the generous samples of Soluplus® polymeric excipient.

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Authors and Affiliations

  1. Department of Chemistry, Oregon State University, 153 Gilbert Hall, Corvallis, OR, USA

    Jeff T. Gautschi

  2. Agere Pharmaceuticals, Inc., Bend, OR, USA

    Jeff T. Gautschi

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  1. Jeff T. Gautschi
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Correspondence to Jeff T. Gautschi .

Editor information

Editors and Affiliations

  1. Department of Pharmaceutics, University of Mississippi School of Phar National Center for Natural Products Res, University, Mississippi, USA

    Michael A. Repka

  2. Pharma Ingredients & Services, BASF Corporation, Tarrytown, New York, USA

    Nigel Langley

  3. Bridgewater, New Jersey, USA

    James DiNunzio

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Gautschi, J. (2013). Nonsink In Vitro Dissolution Testing of Amorphous Solid Dispersions. In: Repka, M., Langley, N., DiNunzio, J. (eds) Melt Extrusion. AAPS Advances in the Pharmaceutical Sciences Series, vol 9. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8432-5_8

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