Improvement of dissolution rates of poorly water soluble APIs using novel spray freezing into liquid technology |
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Authors: | Hu Jiahui Rogers True L Brown Judith Young Tim Johnston Keith P Williams Robert O |
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Institution: | (1) Division of Pharmaceutics, College of Pharmacy (Mail Stop A1920), The University of Texas at Austin, Austin, Texas, 78712;(2) Present address: The Dow Chemical Company, Midland, Michigan, 48674;(3) Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas, 78712 |
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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 m. 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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Keywords: | danazol carbamazepine spray freezing into liquid dissolution stability |
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