热熔挤出技术制备茴三硫固体分散体

Preparation of Anethol trithione solid dispersions by hot-melt extrusion technology

目的制备茴三硫固体分散体。方法分别以Plasdone S630和Poloxamer 188为载体,采用热熔挤出法制备了茴三硫固体分散体并考察两种载体的增溶效果,用差示扫描量热法和X射线粉末衍射法对固体分散体进行了表征,并考察了40℃/75%RH加速实验6个月时的溶出度。结果溶出率大小为:茴三硫-Plasdone S630>胆维他>茴三硫-Poloxamer 188>物理混合物,以Plasdone S630为载体时,药物以无定形或分子状态存在于固体分散体中,以Poloxamer 188为载体时,药物以晶体状态存在于固体分散体中,溶出度稳定性Plasdone S630优于Poloxamer 188。结论 Plasdone S630更适合作为热熔挤出法制备茴三硫固体分散体的载体。

OBJECTIVE To prepare anethol trithione（ATT） solid dispersions.METHODS The anethol trithione solid dispersions with Plasdone S630 or Poloxamer as carriers were prepared by hot-melt extrusion method.The solid dispersions were characterized by differential scanning calorimetry（DSC）,X-ray powder diffraction（XRPD）.The in vitro dissolutions of ATT tablets at an initial 6 months storage under the condition of 40 ℃/75% RH were investigated.RESULTS The order of dissolution rates were observed：ATT-Plasdone S630Danweita（reference tablets）ATT-Poloxamer 188physical mixture.DSC and XRPD showed that the drug was present as amorphous or molecule state in Plasdone S630,as crystalline in Poloxamer 188.Stability of dissolution profiles showed that ATT-Plasdone S630 tablets were more stable than ATT-Poloxamer 188 tablets.CONCLUSION Plasdone S630 is a better selection for hot-melt extrusion method to prepare of anethol trithione as solid dispersions carrier.