Improvement of dissolution rates of poorly water soluble APIs using novel spray freezing into liquid technology.
OBJECTIVE
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.
Hu
Jiahui
J
Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 78712, USA.
Rogers
True L
TL
Brown
Judith
J
Young
Tim
T
Johnston
Keith P
KP
Williams
Robert O
RO
D004339:Drug Compounding; D005615:Freezing; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D014867:Water / Q000737:chemistry*
D004364:Pharmaceutical Preparations; D014867:Water