화학공학소재연구정보센터
Industrial & Engineering Chemistry Research, Vol.48, No.11, 5302-5309, 2009
Particle Size and Bulk Powder Flow Control by Supercritical Antisolvent Precipitation
The purpose of this study was to use silicas for controlling the particle size of a poorly soluble drug in the micrometer to submicrometer range and enhancing the flowability of those particles in a supercritical fluid process. The concept used consists in entrapping a fast precipitated drug into the silica pores and drying the resulting particles fast enough to avoid particle growth and ensure proper size control. Because silica will also enhance the bulk density, it will help in inducing higher flowability to the final product. To prove this concept, a suspension containing a poorly soluble drug and silica was processed using the batch gas antisolvent (GAS) method. Griseofulvin (GF) was used as a model of a poorly water-soluble drug substance, and two types of silica with different pore size and particle size, respectively, were tested. Each experiment was performed at various drug/silica ratios to determine the optimal ratio for particle size control. The products of each experiment were then analyzed using optical microscopy, X-ray powder diffraction (XRPD), and scanning, electron microscopy (SEM). In addition, differential scanning calorimetric tests and dissolution rate studies were performed. Increasing the drug/silica ratio results in more pronounced particle size reduction and is accompanied by a change in drug particle morphology. The produced powders with silica showed enhanced flowability by visual inspection with the naked eye when compared to the neat drug. However, the available data shows that the silica has strong affinity with GF particles and affects the dissolution profile even though GF particle size is reduced. Kinetics instead of thermodynamics seems to be the controlling parameter for GF particles. All the experiments in this work were conducted in batch process mode, and further exploration is planned using the continuous supercritical antisolvent (SAS) process. Quantitative analysis of flowability is also part of the future work.