Nano-mixing of dipyridamole drug and excipient nanoparticles by sonication in liquid CO2

Nanoparticles (about 200 nm thick and 600–12000 nm long flakes) of dipyridamole, a poorly water-soluble anti-thrombosis drug, are produced by supercritical antisolvent solvent with enhanced mass transfer method. Applicability of sonication in liquid CO₂ for mixing of drug and excipient nanoparticles is demonstrated for several binary mixtures 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 mixtures of dipyridamole and excipient particles are sonicated in liquid carbon dioxide. The effects of ultrasonic energy, amplitude, and component weight ratio are studied for the binary mixtures. Characterization of mixing is done using several methods. Scanning electron microscopy is used as a primary method for microscopic analysis. Two macroscopic effects, drug dissolution and blend homogeneity (relative standard deviation), are used to characterize mixing quality of drug/lactose mixture. Results of drug dissolution and blend homogeneity show effectiveness of the proposed mixing method for fine size particles. Material handling properties of drug/silica and lactose/silica mixtures were examined. Upon mixing, the handling properties are significantly improved as measured by compressibility index and Hausner ratio. Liquid CO₂ offers an environmentally benign media for mixing. In addition, the mixture obtained does not contain any residual solvent as compared to the sonication in organic liquids. Upon depressurization, CO₂ is easily removed from the mixture providing a facile recovery of the product.