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摘要
The poor dissolution behaviour of solid drugs in biological environment leads to a low bioavailability. However, the dissolution rate of such drugs can be enhanced dramatically by reduction of the particle size. At present, supercritical fluid based particle size reduction processes are gaining in importance in pharmaceutical technology. For the design of such particle formation processes and the determination of their best operating conditions the knowledge of phase equilibrium and solute solubility in a supercritical fluid is essential. Today, models based on equations of state, together with different mixing rules, are most widely used to correlate and predict the solubility in supercritical fluids. Therefore the accurate knowledge of the required solute data, such as critical parameters, acentric factor, solid molar volume, and sublimation pressure of the solutes is essential. However, the common, non-equation of state based group-contribution methods are mostly empirical and often lead to inconsistent and unreliable results. Thus, due to the lack of information on these data, density-based models are often used for the correlation of experimental solubility data. In this investigation, the solubility of Salicylic acid, of S-Naproxen, of RS-Ibuprofen and of Phytosterol in CO2 is correlated by different methods: two methods for the pressure-solubility correlation and two methods for the density-solubility correlation. In addition, the influence of solute data predicted by different group-contribution methods is investigated. With the exception of S-Naproxen all systems investigated can be modelled sufficient well with a non-cubic equation of state while a cubic equation of state gives less accurate results. In addition, it is shown that for the solutes investigated, the equation of state based method is very sensitive to the values of the sublimation pressure.
- 出版日期2010-12
