Stabilizing dispersions of hydrophobic drug molecules using cellulose ethers during anti-solvent synthesis of micro-particulates

Anti-solvent synthesis of micro-scale drug particles with simultaneous suspension stabilization using different cellulose ethers and a surfactant (SDS) is reported. The process was very effective under low power ultrasonic agitation. The mean diameter of the small particles grew with time, while the overall particle size distribution showed a decrease in average particle size due to sedimentation. The result showed that a combination of cellulose ether and SDS reduced the average particle size more effectively than either only cellulose ether or SDS. The sedimentation rate was also the lowest when both the cellulose ether and SDS were used. At the end of nine hours, as much as 74.6% of the drug Fencifibrate, and 56.0% of the drug griseofulvin remained in stable suspension in drug/HPMC/SDS systems. Zeta potential measurements showed that the suspensions were close to agglomeration rather than thermodynamically stable. Melting point measurements showed that cellulose ether was not a major component of the particle, while scanning electron microscopy revealed particle shapes and degree of the agglomeration. Raman spectroscopy also confirmed the presence of the drug molecule in these crystals. (C) 2008 Elsevier B.V. All rights reserved.