Liao Jin-Bin, Liang Yong-Zhuo, Chen Yun-Long, Xie Jian-Hui, Liu Wei-Hai, Chen Jian Nan, Lai Xiao-Ping, Su Zi-Ren
School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China. ; Guangdong Second Province Hospital of Traditional Chinese Medicine, Guangzhou 510095, P. R. China.
School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
Iran J Pharm Res. 2015 Winter;14(1):15-26.
The present study investigates the possibility of using poloxamers as solubility and dissolution rate enhancing agents of poorly water soluble bioactive constituent patchouli alcohol (PA) that can be used for the preparation of immediate release pellets formulation. Two commercially available grades poloxamer 188 (P 188) and poloxamer 407 (P 407) were selected, and solid dispersions (SDs) containing different weight ratio of PA and poloxamers, and the combination of P 188 and P 407 as dispersing carriers of ternary solid dispersions (tSDs) were prepared by a low temperature melting method and solidified rapidly by dropping into the 10-15 °C condensing agent atoleine. Both PA/P 188 and PA/P 407 binary solid dispersions (bSDs) could remarkably promote the dissolution rate of PA, increasing approximately 16 times in bSDs with poloxamers in comparison with pure PA within 180 min. P188 contributed to a faster dissolution rate than P 407, however, P 407 had a better solubility. It is interesting to note that the incorporation of P 188 in PA/P 407 bSD pellets could strongly enhance the dissolution rate of PA. DSC and FTIR were used to explore the characteristics of PA-SD pellets. The enhancement of dissolution from the SDs may be attributed partly to the reduction in particle size in PA crystalline due to the formation of eutectic system with poloxamers. Moreover, a simple, accurate in-vitro dissolution test method for volatility drug was established, and the process of PA-SD pellets preparation was simple, rapid, cost effective, uncomplicated and potentially scalable.
本研究探讨了使用泊洛沙姆作为难溶性生物活性成分广藿香醇(PA)的溶解度和溶出速率增强剂的可能性,该成分可用于制备速释微丸制剂。选择了两种市售等级的泊洛沙姆188(P 188)和泊洛沙姆407(P 407),通过低温熔融法制备了含有不同重量比的PA和泊洛沙姆的固体分散体(SDs),以及将P 188和P 407组合作为三元固体分散体(tSDs)的分散载体,并通过滴入10 - 15°C的冷凝剂液状石蜡中快速固化。PA/P 188和PA/P 407二元固体分散体(bSDs)均能显著提高PA的溶出速率,与纯PA相比,含泊洛沙姆的bSDs在180分钟内溶出速率提高了约16倍。P188比P 407有助于更快的溶出速率,然而,P 407具有更好的溶解度。值得注意的是,在PA/P 407 bSD微丸中加入P 188可强烈提高PA的溶出速率。采用差示扫描量热法(DSC)和傅里叶变换红外光谱法(FTIR)研究了PA-SD微丸的特性。SDs溶出度的提高可能部分归因于与泊洛沙姆形成低共熔体系导致PA晶体粒径减小。此外,建立了一种简单、准确的挥发性药物体外溶出试验方法,PA-SD微丸的制备过程简单、快速、经济高效、不复杂且具有潜在的可扩展性。