Spray freezing into liquid (SFL) particle engineering technology to enhance dissolution of poorly water soluble drugs: organic solvent versus organic/aqueous co-solvent systems

Spray freezing into liquid (SFL) particle engineering technology to enhance dissolution of poorly water soluble drugs: organic solvent versus organic/aqueous co-solvent systems
November 2003
Jiahui Hu, a, Keith P. Johnston, b, and Robert O. Williams, III, a
a Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Mail Stop A1920, Austin, TX 78712, USA
b Department of Chemical Engineering, The University of Texas at Austin, Austin, TX 78712, USA
European Journal of Pharmaceutical Sciences Volume 20, Issue 3 , November 2003, Pages 295-303
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Abstract
A spray freezing into liquid (SFL) particle engineering technology has been developed to produce micronized powders to enhance the dissolution of poorly water soluble active pharmaceutical ingredients (APIs). Previously, a tetrahydrofuran (THF)/water co-solvent was used as the solution source in the SFL process. In the present study, an organic system was developed to further enhance the properties of particles produced by SFL. The influence of solution type (e.g. organic versus organic/water) on the physicochemical properties of SFL powders was investigated and compared. The physicochemical properties of SFL carbamazepine (CBZ)/poloxamer 407/PVP K15 (2:1:1 ratio) powders were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), particle size distribution, surface area analysis, contact angle measurement, Karl?Fisher (KF) titration, gas chromatography (GC) analysis, HPLC analysis, and dissolution testing. The CBZ loading in the feed solution of the SFL acetonitrile system was 2.2% (w/w), which was greater than 0.22% (w/w) loading of the THF/water co-solvent system. XRD results indicated CBZ was amorphous in SFL powders produced by either system. SEM micrographs indicated that SFL powders from acetonitrile appeared less porous with a smaller primary particle size than particles from the co-solvent. The M50 (50% cumulative percent undersize) of micronized powder from the SFL acetonitrile system and the THF/water co-solvent system with 0.22% CBZ loading were 680 nm and 7.06 small mu, Greekm, respectively. The surface area of SFL powders from the acetonitrile and co-solvent systems were 12.89 and 13.31 m2/g, respectively. The contact angle of the SFL powders against purified water was about 35? for both systems. The SFL powders from both systems exhibited similar and significantly enhanced dissolution rates compared to the bulk CBZ. Acetonitrile was an effective alternative solvent to THF/water co-solvent for use with the SFL micronization process to produce free flowing particles containing CBZ with significantly enhanced wetting and dissolution properties.