Liang Qi, Wang Yi-Ru, Deng Yue-Yi
College of Pharmacy,Guilin Medical University Guilin 541004,China.
Zhongguo Zhong Yao Za Zhi. 2019 Aug;44(15):3305-3311. doi: 10.19540/j.cnki.cjcmm.20190516.301.
To enhance in vitro dissolution of Cur by preparing Cur solid dispersions. The ability of HPMCAS-HF,HPMCAS-MF,HPMCAS-LF and PVPK30 to maintain supersaturated solution was investigated by supersaturation test. Amorphous solid dispersions were prepared by the solvent-evaporation method. The prepared samples were characterized using infrared spectroscopy( IR) and differential scanning calorimetry( DSC),and in vitro dissolution was investigated. DSC and IR results showed that in 1 ∶3 and 1 ∶9 solid dispersions,Cur was amorphously dispersed in the carrier,and the interaction existed between drug and carrier. The supersaturation test showed that the order of the ability of polymer to inhibit crystallization of Cur was MF>HF>LF>K30. The dissolution results showed that Cur-K30 amorphous solid dispersion had the highest drug release rate; Cur-K30 and Cur-LF amorphous solid dispersions had a quicker but not stable dissolution rate,and the drug concentration decrease after 4 h; Cur-MF and Cur-HF solid dispersions had a low dissolution,which however increased steadily,attributing to the strong ability of the polymers to inhibit the crystallization of Cur. HPMCAS could inhibit the degradation of Cur better than K30,especially MF and HF. The amorphous solid dispersions of cur significantly enhanced the dissolution of Cur and improved the chemical stability of Cur. This study can provide a basis for the rational selection of the polymer used for Cur solid dispersion.
通过制备姜黄素(Cur)固体分散体来提高其体外溶出度。通过过饱和试验研究了羟丙基甲基纤维素琥珀酸酯高取代度(HPMCAS-HF)、中取代度(HPMCAS-MF)、低取代度(HPMCAS-LF)和聚乙烯吡咯烷酮K30(PVPK30)维持过饱和溶液的能力。采用溶剂蒸发法制备无定形固体分散体。使用红外光谱(IR)和差示扫描量热法(DSC)对制备的样品进行表征,并研究其体外溶出度。DSC和IR结果表明,在1∶3和1∶9的固体分散体中,Cur以无定形形式分散在载体中,药物与载体之间存在相互作用。过饱和试验表明,聚合物抑制Cur结晶能力的顺序为MF>HF>LF>K30。溶出结果表明,Cur-K30无定形固体分散体的药物释放速率最高;Cur-K30和Cur-LF无定形固体分散体的溶出速率较快但不稳定,4小时后药物浓度下降;Cur-MF和Cur-HF固体分散体的溶出度较低,但呈稳步上升趋势,这归因于聚合物抑制Cur结晶的能力较强。HPMCAS比K30更能抑制Cur的降解,尤其是MF和HF。Cur的无定形固体分散体显著提高了Cur的溶出度并改善了Cur的化学稳定性。本研究可为Cur固体分散体所用聚合物的合理选择提供依据。