(157g) 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 (SAS-EM) method. Mixing of drug nanoparticles (in order to prevent reagglomeration during storage and to improve the handling properties) is carried out with three different excipients: silica nanoparticles, lactose microparticles, and polyvinylpyrrolidone (PVP) nanoparticles. To intimately mix at nanoscale, macro mixtures of dipyridamole and excipient particles are sonicated in liquid carbon dioxide. Effect of ultrasonic energy, amplitude, and component weight ratio were studied for binary mixtures. Qualitative analysis of deagglomeration and mixing of drug/silica, drug/PVP, and lactose/silica mixtures were done using scanning electron microscopy (SEM) while drug/lactose mixture was analyzed using both SEM and blend homogeneity (i.e., relative standard deviation in the drug concentration). 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 easily evaporates off the mixture providing a facile recovery of the product.