Jin Gang, Ngo Hai V, Cui Jing-Hao, Wang Jie, Park Chulhun, Lee Beom-Jin
College of Pharmacy, Ajou University, Suwon 16499, Korea.
School of Chemical and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin 132022, China.
Pharmaceutics. 2021 May 5;13(5):662. doi: 10.3390/pharmaceutics13050662.
This study aimed to investigate the role of micellization of sodium lauryl sulfate (SLS) in poloxamer 407 (POX)-based solid dispersions (POX-based SDs) using the anti-solvent method in enhancing the dissolution rate of practically water-insoluble cilostazol (CLT). Herein, SLS was incorporated into CLT-loaded SDs, at a weight ratio of 50:50:10 of CLT, POX, and SLS by three different methods: anti-solvent, fusion (60 °C), and solvent (ethanol) evaporation. The SDs containing micellar SLS in the anti-solvent method were superior in the transformation of the crystalline form of the drug into a partial amorphous state. It was notable that there was an existence of a hydrophobic interaction between the surfactant and the hydrophobic regions of polymer chain via non-covalent bonding and the adsorption of micellar SLS to the POX-based SDs matrix. Moreover, SLS micellization via the anti-solvent method was effectively interleaved in SDs and adhered by the dissolved CLT, which precluded drug particles from aggregation and recrystallization, resulting in improved SD wettability (lower contact angle) and reduced particle size and dissolution rate. In contrast, SDs without micellar SLS prepared by the solvent method exerted drug recrystallization and an increase of particle size, resulting in decreased dissolution. Incorporation of surfactant below or above critical micellar concentration (CMC) in SDs using the anti-solvent method should be considered in advance. Dissolution results showed that the pre-added incorporation of micellar SLS into POX-based SDs using the anti-solvent method could provide a way of a solubilization mechanism to enhance the dissolution rate of poorly water-soluble drugs.
本研究旨在利用抗溶剂法研究月桂醇硫酸酯钠（SLS）在泊洛沙姆407（POX）基固体分散体（POX基SDs）中的胶束化作用，以提高实际水不溶性西洛他唑（CLT）的溶解速率。在此，通过三种不同方法将SLS以CLT、POX和SLS重量比为50:50:10的比例掺入载有CLT的SDs中：抗溶剂法、熔融法（60℃）和溶剂（乙醇）蒸发法。抗溶剂法制备的含胶束SLS的SDs在将药物晶型转变为部分无定形状态方面表现更优。值得注意的是，表面活性剂与聚合物链的疏水区域之间通过非共价键存在疏水相互作用，且胶束状SLS吸附于POX基SDs基质上。此外，通过抗溶剂法形成的SLS胶束有效地穿插在SDs中，并被溶解的CLT附着，这阻止了药物颗粒的聚集和重结晶，从而改善了SDs的润湿性（降低接触角），减小了粒径并提高了溶解速率。相比之下，通过溶剂法制备的不含胶束SLS的SDs出现了药物重结晶和粒径增大的情况，导致溶出度降低。使用抗溶剂法时，应提前考虑在SDs中加入低于或高于临界胶束浓度（CMC）的表面活性剂。溶出结果表明，采用抗溶剂法预先将胶束状SLS掺入POX基SDs中，可为提高难溶性药物的溶解速率提供一种增溶机制。
