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.
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.