摘要
本研究分别以羟丙甲纤维素醋酸琥珀酸酯[HPMCAS (MF)、HPMCAS (HF)]、甲基丙烯酸氯化三甲胺基乙酯共聚物(Eudragit L100-55、Eudragit S100)、羟丙甲纤维素邻苯二甲酸酯(HPMC P55)为聚合物载体,采用热熔挤出技术制备单载体固体分散体,进一步加入不同比例的表面活性剂制备二元体系固体分散体,利用差示扫描量热和X 射线粉末衍射法对其物理状态进行表征,并通过体外模拟胃肠液过饱和溶出试验研究表面活性剂的种类及浓度的析晶抑制能力。结果表明,含有表面活性剂二元载体的析晶抑制能力显著高于单一的聚合物载体。不同表面活性剂的析晶抑制能力为:维生素E 聚乙二醇1000 琥珀酸酯(TPGS)>聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇接枝共聚物(Soluplus)>泊洛沙姆188(poloxamer 188)>十二烷基硫酸钠(SDS)。对于同一种表面活性剂而言,随着表面活性剂浓度不断增加,析晶抑制能力逐渐增加,但增加到一定程度后其析晶抑制能力趋于稳定。本研究构建了基于聚合物-表面活性剂二元体系的固体分散体,更好地解决了弱碱性难溶药物在胃肠道析晶的问题,为无定形固体分散体的产业化提供了理论指导。
In this study, hypromellose acetate succinate (HPMCAS MF and HF), Eudragit?(L100-55 and S100), and hypromellose (HPMC P55) were used as the polymer carriers to prepare solid dispersions by hot melt extrusion method. Then, different surfactants were added into above systems to prepare solid dispersions based on polymer-surfactant binary carriers. The physical states of the obtained samples were characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD), and the in vitro dissolution test under supersaturated condition was employed to evaluate the crystallization inhibition abilities of different surfactants. The results showed that the crystallization inhibition ability of binary carriers containing surfactants was significantly higher than that of single polymer carrier. And the crystallization inhibition ability was highly dependent on the surfactant types, which was in the sequence of D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)>polyvinyl caprolactam-polyvinyl acetatepolyethylene glycol graft copolymer (Soluplus)>poloxamer 188> dodecyl sodium sulfate (SDS). Additionally, for the same surfactant, the crystallization inhibition ability increased with the increase in surfactant proportion, and the ability tented to be stable after surfactant proportion increasing to a certain level. Amorphous solid dispersion based on polymersurfactant binary system constitutes a potential tool to solve the crystallization problem of poorly water-soluble weakly basic drugs in gastrointestinal tract, which constructs the theoretical framework for the industrialization of amorphous solid dispersions.
作者
杨蓓蓓
冯地桑
潘昕
权桂兰
吴传斌
YANG Beibei;FENG Disang;PAN Xin;QUAN Guilan;WU Chuanbin(School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou 510006)
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2019年第9期993-1004,共12页
Chinese Journal of Pharmaceuticals
作者简介
杨蓓蓓(1996-),女,硕士研究生,专业方向:缓控释给药系统及经皮给药系统研究。Tel:15626428737,E-mail:1007957882@qq.com;通讯作者:权桂兰(1988-),女,副研究员,从事缓控释给药系统及新型多孔药物递送载体的研究。Tel:020-39943115,E-mail:quanglan@mail.sysu.edu.cn.
