聚合物/表面活性剂二元载体的固体分散体提高普罗布考的溶出度

Improved dissolution of probucol via solid dispersion with polymer/surfactant binary carrier

目的制备以普罗布考为模型药物的固体分散体,以聚合物与表面活性剂为二元载体材料,提高药物溶出度。方法以聚维酮PVP K30、Kollidon VA64、Eudragit E100和Soluplus等聚合物,非离子型表面活性剂Cremophor RH40、D-α-生育酚聚乙二醇1000琥珀酸酯等为载体材料,采用溶剂挥发法制备单一载体或聚合物/表面活性剂二元载体的普罗布考固体分散体。分别在漏槽和非漏槽条件下考察固体分散体的溶出度,差示扫描量热法表征固体分散体中药物结晶状态。结果单一载体普罗布考固体分散体在非漏槽条件下的溶出度均不理想。适宜的聚合物与表面活性剂组合的二元载体固体分散体能明显增加非漏槽条件下的溶出度。热分析结果显示,药物在固体分散体中以非结晶状态存在。非漏槽条件下,VA64/RH40或聚维酮/RH40二元载体固体分散体在介质中形成纳米分散液,溶出度显著增加;而Soluplus/RH40二元载体固体分散体在介质中聚集沉淀,导致溶出度很低。结论聚合物/表面活性剂二元载体有利于提高难溶性药物的溶出,Kollidon VA64/RH40二元载体固体分散体显著提高普罗布考在非漏槽条件的溶出度。

Objective To improve the in vitro dissolution of water-insoluble drug probucol by the solid dispersion made of binary carriers composed of polymers and surfactants. Methods Polymers（ PVP K30,Kollidon VA 64,Eudragit E100,and Soluplus,etc） and nonionic surfactants（ Cremophor RH40,and TPGS,etc）,or polymer-surfactant combinations were used as the single or binary carrier of probucol solid dispersion（ PB-SD）,and the solvent evaporation method was utilized to prepare drug loaded solid dispersions. In vitro drug dissolution of probucol solid dispersions was tested under sink or non-sink conditions, respectively. The solid dispersions were characterized by DSC method. Results The results showed that the dissolution rate of probucol solid dispersions with single carrier under non-sink condition was relatively low. The dissolution of PB-SD either under sink condition or under non-sink condition was improved by introducing surfactant into the binary carrier and elaborately selecting the combination of polymer and surfactant. DSC analysis indicated that probucol was embedded as non-crystalline state inside the solid dispersions of VA64/RH40 and Soluplus/RH40 binary carriers. Under non-sink condition,VA64/RH40 or PVP K30/RH40 binary carrier solid dispersion could form nano-liquid dispersion after reconstituted in dissolution media and thus improved the dissolution of PB,while Soluplus/RH40 binary carrier solid dispersion aggregated and precipitated out with only about 5% dissolved within 60 min. Conclusions Polymer/surfactant binary carrier is effective in improving the dissolution of water-insoluble drugs. VA64/RH40 binary carrier solid dispersion can greatly improve the dissolution of probucol.