Angela Mary Barrett1, Fariba Dehghani, Neil R Foster. 1. School of Chemical Sciences and Engineering, The University of New South Wales, Sydney, NSW 2052, Australia. a.barrett@student.unsw.edu.au
Abstract
PURPOSE: The purpose of this study was to increase the dissolution rate of the poorly water soluble, antifungal drug Itraconazole. METHODS: Itraconazole was successfully micronized using both the gas antisolvent (GAS) and aerosol solvent extraction systems (ASES) using Acetone as the solvent. The affects of operating conditions such as temperature, pressure and solvent choice on variables such as morphology, particle size and dissolution were investigated. The influence of temperature in the range 25 to 40 degrees C and pressure between 90 and 190 bar were investigated. RESULTS: Solvent choice was found to have the largest affect on particle production, with acetone found to be the optimal solvent choice when compared with dimethyl formamide (DMF), tetrahydrofuran (THF) and dichloromethane (DCM). Itraconazole particles with an average particle size of 6.9 microm were formed at the optimal ASES processing conditions of 40 degrees C and 190 bar. More significantly, in the first 100 minutes of dissolution 71.1% of the dense gas processed itraconazole was dissolved compared with 52.5% of Sporonox (the commercially available formulation) and 14.6% of the unprocessed material. Additional studies demonstrated that the formation of an itraconazole/PEG composite resulted in a 6-fold increase in dissolution rate in the first 100 min, to 89.8%, when compared to the unprocessed material. CONCLUSIONS: Using ASES, microparticles of itraconazole were produced with an increased dissolution rate compared with raw material and commercially available product.
PURPOSE: The purpose of this study was to increase the dissolution rate of the poorly water soluble, antifungal drug Itraconazole. METHODS:Itraconazole was successfully micronized using both the gas antisolvent (GAS) and aerosol solvent extraction systems (ASES) using Acetone as the solvent. The affects of operating conditions such as temperature, pressure and solvent choice on variables such as morphology, particle size and dissolution were investigated. The influence of temperature in the range 25 to 40 degrees C and pressure between 90 and 190 bar were investigated. RESULTS: Solvent choice was found to have the largest affect on particle production, with acetone found to be the optimal solvent choice when compared with dimethyl formamide (DMF), tetrahydrofuran (THF) and dichloromethane (DCM). Itraconazole particles with an average particle size of 6.9 microm were formed at the optimal ASES processing conditions of 40 degrees C and 190 bar. More significantly, in the first 100 minutes of dissolution 71.1% of the dense gas processed itraconazole was dissolved compared with 52.5% of Sporonox (the commercially available formulation) and 14.6% of the unprocessed material. Additional studies demonstrated that the formation of an itraconazole/PEG composite resulted in a 6-fold increase in dissolution rate in the first 100 min, to 89.8%, when compared to the unprocessed material. CONCLUSIONS: Using ASES, microparticles of itraconazole were produced with an increased dissolution rate compared with raw material and commercially available product.