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Improvement of Dissolution Rates of Poorly Water Soluble APIs Using Novel Spray Freezing into Liquid Technology

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Abstract

Purpose. To develop and demonstrate a novel particle engineering technology, spray freezing into liquid (SFL), to enhance the dissolution rates of poorly water-soluble active pharmaceutical ingredients (APIs).

Methods. Model APIs, danazol or carbamazepine with or without excipients, were dissolved in a tetrahydrofuran/water cosolvent system and atomized through a nozzle beneath the surface of liquid nitrogen to produce small frozen droplets, which were subsequently lyophilized. The physicochemical properties of the SFL powders and controls were characterized by X-ray diffraction, scanning electron microscopy (SEM), particle size distribution, surface area analysis, contact angle measurement, and dissolution.

Results. The X-ray diffraction pattern indicated that SFL powders containing either danazol or carbamazepine were amorphous. SEM micrographs indicated that SFL particles were highly porous. The mean particle diameter of SFL carbamazepine/SLS powder was about 7 μm. The surface area of SFL danazol/poloxamer 407 powder was 11.04 m2/g. The dissolution of SFL danazol/poloxamer 407 powder at 10 min was about 99%. The SFL powders were free flowing and had good physical and chemical stability after being stored at 25°C/60%RH for 2 months.

Conclusions. The novel SFL technology was demonstrated to produce nanostructured amorphous highly porous particles of poorly water soluble APIs with significantly enhanced wetting and dissolution rates.

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Author notes

  1. Tim Young

    Present address: The Dow Chemical Company, Midland, Michigan, 48674

Authors and Affiliations

  1. Division of Pharmaceutics, College of Pharmacy (Mail Stop A1920), The University of Texas at Austin, Austin, Texas, 78712

    Jiahui Hu, True L. Rogers, Judith Brown & Robert O. Williams III

  2. Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas, 78712

    Tim Young & Keith P. Johnston

Authors
  1. Jiahui Hu
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  2. True L. Rogers
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  3. Judith Brown
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  4. Tim Young
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  5. Keith P. Johnston
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  6. Robert O. Williams III
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Correspondence to Robert O. Williams III.

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Hu, J., Rogers, T.L., Brown, J. et al. Improvement of Dissolution Rates of Poorly Water Soluble APIs Using Novel Spray Freezing into Liquid Technology. Pharm Res 19, 1278–1284 (2002). https://doi.org/10.1023/A:1020390422785

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