Biological Nano-Particle Formation by Compressed Fluids Technology
Seyed Ali Vaziri Yazdi Sr., Azad Research & Science university Branch, Chemical Engineering, Tehran, Iran, Mohammad Mehdi Akbarnejad, Tehran, Research Institute of Petroleum Industry of Iran, Tehran, Iran, Ali Akbar Seyfkordi, Chemical Engineering, Sharif University, Tehran, Iran and Fatemeh Zabihi, Chemical Engineering, Azad Research & Science university, Tehran, Iran

Many of foods, complements and drugs which enters into human's body orally, are made of water insoluble components. A significant part of discovered biological entities are poorly water soluble or lipophilic compounds. For drugs of low water solubility, particle size, size distribution and the resulting surface area could have a significant effect on dissolution rate which is the limiting factor in most cases, because drugs with low lipophilicity can

not permeate biomembrane quickly. Various techniques have been developed to produce nano/micro particles, including micronization, surfactant-aid dispersion, the use of organic solvents, emulsions and microemulsions, solid dispersion technology and carriers based on polymers and liposomes, etc. However, some of these techniques introduce various problems or limitations such as broad distribution in particle size, excessive solvent use and disposal, thermal and/or chemical degradation of biological substances and contamination with unwanted residues. The precipitation of organic particles from Compressed Fluids (CF) by expansion (SCFE) has become an interesting alternative in contrast to the other methods for converting solid organics to nano-powders. In this method, the substance of interest, generally a nonvolatile solute is first dissolved in supercritical fluid. The rapid expansion of supercritical mixtures can therefore result in very high supersaturation. This combination of large supersaturation and uniform conditions favors small particles and narrow size distributions and is a distinguishing feature of this process. The rapid solute pressure drop occurring during supercritical solution expansion through a nozzle, leads to solute nucleation and particle growth which may be impacted by a variety of experimental parameters. A lot of experimental results about this subject, present some offers to modify particles properties in this method. These results sometimes are accordant and in some other cases are not, so none of them gives fine tuning data to use for modifying particles size and morphology. Carbon Dioxide is very attractive as a supercritical fluid, especially for heat-sensitive biological materials. Because it is non-toxic, chemically inert and its critical pressure and temperature are low relatively. In this work, some experimental results for a biological model component are shown. The process variables are nozzle temperature (TN) and extraction pressure (PExt). We considered the “Mean particles diameter” as our reference parameter to compare different runs products. After each run the particles size was measured directly by SEM and mean particle size was calculated by mathematical methods. All experiments were accomplished through RESS (Rapid Expansion Supercritical Solvents) process that is usually applied for organic compounds, and size distribution curves were drown for each run based on particle sizes which measured by SEM analysis. All process parameters except nozzle temperature and extraction pressure held constant and their effects on particle mean size was determined. The most important limitation of RESS process is high pressure apparatus set up costs. Therefore we studied the process efficiencies in lower pressures of Carbon Dioxide supercritical area. Results shows that in selected pressure rang, low temperatures are better to produce fine, amorph and uniform particles. In higher temperatures, density drop and precipitation in nozzle path leads to larger particles with high crystallity. In addition we compared the importance of nozzle temperature and extraction pressure in products quality. Results show that in our experimental temperature range, which depends on the interested biological substance physical properties, low extraction pressures cause nozzle temperature become very effective on particles appearance. This impact gradually gets weak by increasing extraction pressure. In high extraction pressures, nozzle temperature has no significant effect.

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Poster Session

The Preliminary Program for SBE's 2nd International Conference on Biomolecular Engineering