Influence of Supercritical Antisolvent Micronization Parameters on Nalmefene HCl Powder Characteristics
Influence of Supercritical Antisolvent Micronization Parameters on Nalmefene HCl Powder Characteristics
复制标题
DOI：
10.1163/156855208x368607
复制
发表时间：
2008
影响因子：
5.2
通讯作者：
R. Adami;E. Järvenpää;L. S. Ossèo;R. Huopalahti
中科院分区：
文献类型：
--
作者：
R. Adami;E. Järvenpää;L. S. Ossèo;R. Huopalahti
超临界抗溶剂沉淀法是一种很有前途的药物微粉化技术。与所有制造过程一样，SA可能会导致固态修饰，形成不需要的多晶型或降解产物，并在最终产品中存在溶剂残留物。研究了SAS工艺参数对盐酸纳美芬粉末性能的影响。以乙醇为液体溶剂，超临界二氧化碳为抗溶剂。微粉化实验在压力130~150bar、温度40~67℃、CO2摩尔分数0.95~0.97之间进行。在不同的操作条件下，通过改变抗溶剂摩尔分数，可以得到结晶度不同、尺寸不同的无定形粒子和不同结晶度的粒子。用高效液相色谱和顶空气相色谱分析验证了微粉化产物的纯度和无残留乙醇。用差示扫描量热法、X射线粉末衍射法和热重分析法研究了微粉化的盐酸纳美芬颗粒的结构特征。微粉化过程没有引起化合物和溶剂残留量低于2p.p.m的产品的降解。得到了。该工艺使盐酸纳美芬从水合状态变为无水状态，在特定条件下也得到了溶剂化形式。
Supercritical antisolvent precipitation (SAS) is a promising technique for the micronization of pharmaceutical compounds. Like all the manufacturing processes, SAS might induce solid-state modifications, the formation of undesired polymorphic forms or degradation products and the presence of solvent residues in the final product. In this work, the influence of SAS process parameters on nalmefene HCl powder characteristics was investigated. Ethanol was used as the liquid solvent and supercritical carbon dioxide as antisolvent. Micronization experiments were performed at pressures of 130 and 150 bar, in the temperature range 40–67°C, and CO2 molar fraction was between 0.95 and 0.97. Amorphous particles and particles with different degrees of crystallinity and different sizes were obtained by varying the antisolvent molar fraction at different operating conditions. High-performance liquid chromatography and headspace gas chromatography analyses were performed to verify the purity of the micronized product and the absence of residual ethanol. The structural characteristics of micronized nalmefene HCl particles were studied by differential scanning calorimetry, X-ray powder diffraction and thermogravimetry analyses. The micronization process did not induce degradation of the compound and a product with a solvent residue less than 2 p.p.m. was obtained. The process induced the modification of nalmefene HCl from hydrated to anhydrous form; at particular conditions a solvate form was also obtained.