72. Sanganwar, Ganesh P.; Gupta, Ram B.. Nano-mixing of dipyridamole drug and excipient nanoparticles by sonication in liquid CO2. Powder Technology (2009), 196(1), 36-49.
Abstract
Nanoparticles (about 200 nm
thick and 600-12,000 nm long flakes) of dipyridamole, a poorly
water-sol. anti-thrombosis drug, are produced by supercrit. antisolvent
solvent with enhanced mass transfer method. Applicability of
sonication in liq. CO2 for mixing of drug and excipient nanoparticles
is demonstrated for several binary mixts. of drug and excipient.
The drug particles are mixed with three different excipients: silica
nanoparticles, lactose microparticles, and polyvinylpyrrolidone
nanoparticles. To intimately mix at nanoscale, macro mixts. of
dipyridamole and excipient particles are sonicated in liq. carbon
dioxide. The effects of ultrasonic energy, amplitude, and
component wt. ratio are studied for the binary mixts.
Characterization of mixing is done using several methods. SEM is
used as a primary method for microscopic anal. Two macroscopic
effects, drug dissoln. and blend homogeneity (relative std. deviation),
are used to characterize mixing quality of drug/lactose mixt.
Results of drug dissoln. and blend homogeneity show effectiveness of
the proposed mixing method for fine size particles. Material
handling properties of drug/silica and lactose/silica mixts. were
examd. Upon mixing, the handling properties are significantly
improved as measured by compressibility index and Hausner ratio.
Liq. CO2 offers an environmentally benign media for mixing. In
addn., the mixt. obtained does not contain any residual solvent as
compared to the sonication in org. liqs. Upon depressurization,
CO2 is easily removed from the mixt. providing a facile recovery of the
product.
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