Micronization of SMZ Drug Using High-gravity Precipitation Process
Date Issued
2007
Date
2007
Author(s)
Lee, Cha-Haung
DOI
zh-TW
Abstract
Abstract
In recent years, pharmaceutical industry becomes the main stream of biotechnology in Taiwan. However, 40% of new drugs have two problems: low solubility and low dissolution rate, and thus low bioavailability. In order to overcome these two problems, one of the most common and effective method was to reduce the drug size. In this research, reaction precipitation method and anti-solvent precipitation method were adopted to reduce the particle size of the drugs in a high-gravity system.
Sulfamethoxazole(SMZ) was chosen as the model drug, which was one kind of sulfonamide antibiotics. It was used as antiseptic to treat respiratory system infection, urinary system infection and intestines infection. Moreover, when it was used as eyewash agent, it could treat conjunctivitis and sand holes.
In this study, when using reaction precipitation method, the effect of operating variables, including additive, nozzle size, disk diameter, rotating speed, aging time, temperature, flow rate, milling condition and reappearance were studied, also solubility and dissolution rate of product were measured. Moreover, when using anti-solvent precipitation method, the effect of operating variables, including additive, temperature, rotating speed, nozzle size and the operation mode, i.e, continuous vs. recycle were studied, also solubility and dissolution rate were measured. Finally, the results obtained from the two methods were compared and discussed.
The particle size of original drugs in this study was about 10~25μm. The particle size of product obtained in the reaction precipitation experiment was between 1~5μm, and a few particles of larger size were present. Adding Tween80 as additive could prevent products from adhering on the surface of disk, and the yield of this method reached 88%. In the anti-solvent precipitation experiment, particle size was also between 1~5μm. The distribution was more uniform because large particles were almost disappeared. When adding Tween80 as additive, the yield of the anti-solvent precipitation method reached 77%. When the operation mode was changed from continuous to recycle mode, the yield reached 83%.
Comparing the samples from the two methods, the particle size were similar to each other, but the particle size distribution was more uniform for anti-solvent precipitation method. Under pH of 1.12, the 90% SMZ from reaction precipitation method were dissolved in 25 minutes, and the 90% SMZ from anti-solvent precipitation method were dissolved in 13 minutes. It showed that anti-solvent precipitation method was better for promoting dissolution rate of SMZ. Addition of HPC to SMZ could raise products dissolution rate. When the amount of HPC added was 10~15wt% of SMZ, 95% SMZ were dissolved in 5 to 6 minutes for both samples.
Subjects
SMZ藥品
微粒化
旋轉盤反應器
反應沉澱
反溶劑沉澱
SMZ drug
micronization
spinning-disk reactor
reaction precipitation
anti-solvent precipitation
Type
thesis
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