Fig. 1. Schematic Representation of a Complex Fluidized-Bed Granulator
1: Exhaust air, 2: bag filter, 3: partition tube, 4: impeller, 5: rotor disc, 6: inlet air, 7: screen, 8: spray nozzle.
Preparation of Fine Particles with Improved Solubility Using a Complex Fluidized-Bed Granulator Equipped with a Particle-Sizing Mechanism
Abstract
A new type of fluidized-bed granulator equipped with a particle-sizing mechanism was used for the preparation of fine particles that improved the solubility of a poorly water-soluble drug substance. Cefteram pivoxyl (CEF) was selected as a model drug substance, and its solution with a hydrophilic polymer, hydroxypropyl cellulose (HPC-L), was sprayed on granulation grade lactose monohydrate (Lac). Three types of treated particles were prepared under different conditions focused on the spraying air pressure and the amount of HPC-L. When the amount of HPC-L was changed, the size of the obtained particles was similar. However, particle size distribution was dependent on the amount of HPC-L. Its distribution became more homogenous with greater amounts of HPC-L, but the particle size distribution obtained by decreasing the spraying air pressure was not acceptable. By processing CEF with HPC-L using a complex fluidized-bed granulator equipped with a particle-sizing mechanism, the dissolution ratio was elevated by approximately 40% compared to that of unprocessed CEF. Moreover, in the dissolution profile of treated CEF, the initial burst was suppressed, and nearly zero order release was observed up to approximately 60% in the dissolution profile. This technique may represent a method with which to design fine particles of approximately 100 µm in size with a narrow distribution, which can improve the solubility of a drug substance with low solubility.
Conclusion
Three types of treated particles were prepared using a complex fluidized-bed granulator equipped with a particle-sizing mechanism under different conditions focused on the spraying air pressure and the amount of HPC-L. When the amount of HPC-L was changed, the size of the obtained particles was similar. However, particle size distribution was dependent on the amount of HPC-L. Its distribution became more homogenous with greater amounts of HPC-L, but the particle size distribution obtained by decreasing the spraying air pressure was not acceptable.
By processing CEF with HPC-L using this device, the dissolution ratio was elevated by approximately 40% compared to that of unprocessed one. Moreover, in the dissolution profile of treated CEF, the initial burst was suppressed, and nearly zero order release was observed up to approximately 60% in the dissolution profile.
The present method is applicable to the design of fine particles of approximately 100 µm in size with a narrow distribution, which improved the solubility of drug substance.
