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 microm. 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 degrees 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.
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 microm. 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 degrees 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.
Authors: N Kondo; T Iwao; H Masuda; K Yamanouchi; Y Ishihara; N Yamada; T Haga; Y Ogawa; K Yokoyama Journal: Chem Pharm Bull (Tokyo) Date: 1993-04 Impact factor: 1.645
Authors: True L Rogers; Ian B Gillespie; James E Hitt; Kevin L Fransen; Cindy A Crowl; Christopher J Tucker; Gary B Kupperblatt; Joe N Becker; Deb L Wilson; Clifford Todd; Charles F Broomall; Jonathan C Evans; Edmund J Elder Journal: Pharm Res Date: 2004-11 Impact factor: 4.200
Authors: True L Rogers; Andrew C Nelsen; Marazban Sarkari; Timothy J Young; Keith P Johnston; Robert O Williams Journal: Pharm Res Date: 2003-03 Impact factor: 4.200
Authors: Esmaeil Biazar; Ali Beitollahi; S Mehdi Rezayat; Tahmineh Forati; Azadeh Asefnejad; Mehdi Rahimi; Reza Zeinali; Mahmoud Ardeshir; Farhad Hatamjafari; Ali Sahebalzamani; Majid Heidari Journal: Int J Nanomedicine Date: 2009-12-29