Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Universitätsstr. 1, 40225 Duesseldorf, Germany.
Int J Pharm. 2012 Jan 17;422(1-2):116-24. doi: 10.1016/j.ijpharm.2011.10.037. Epub 2011 Oct 21.
Solid lipid extrudates with the model drug praziquantel were produced with chemically diverse lipids and investigated regarding their dissolution behaviour in different media. The lipids used in this study were glyceryl tripalmitate, glyceryl dibehenate, glyceryl monostearate, cetyl palmitate and solid paraffin. Thermoanalytical and dissolution behaviour was investigated directly after extrusion and after 3 and 6 months open storage at 40°C/75% RH. Dissolution studies were conducted in hydrochloric acid (HCl) pH 1.2 with different levels of polysorbate 20 and with a biorelevant medium containing pancreatic lipase, bile salts and phospholipids. Furthermore, the impact of lipid digestion on drug release was studied using in vitro lipolysis. The release of praziquantel from cetyl palmitate and glyceryl monostearate in the biorelevant medium was much faster than in HCl, whereas there was hardly any difference for the other lipids. It was shown that drug release from glyceryl monostearate matrices is driven by both solubilisation and enzymatic degradation of the lipid, whereas dissolution from cetyl palmitate extrudates is dependent only on solubilisation by surfactants in the medium. Moreover, storage influenced the appearance of the extrudate surface and the dissolution rate for all lipids except solid paraffin.
采用具有不同化学性质的脂质制备了载有模型药物吡喹酮的固体脂质挤出物,并研究了它们在不同介质中的溶解行为。本研究中使用的脂质有三棕榈酸甘油酯、二硬脂酸甘油酯、单硬脂酸甘油酯、十六烷酸棕榈酯和固体石蜡。直接在挤出后以及在 40°C/75%相对湿度下开放储存 3 个月和 6 个月后,对其进行热分析和溶解行为研究。在盐酸(HCl)pH 1.2 中进行了溶解研究,其中含有不同水平的聚山梨酯 20 和含有胰腺脂肪酶、胆汁盐和磷脂的生物相关介质。此外,还使用体外脂肪酶解研究了脂质消化对药物释放的影响。在生物相关介质中,从十六烷酸棕榈酯和单硬脂酸甘油酯中释放的吡喹酮比在 HCl 中快得多,而对于其他脂质几乎没有差异。结果表明,单硬脂酸甘油酯基质中药物的释放是由脂质的增溶和酶降解共同驱动的,而十六烷酸棕榈酯挤出物的溶解则仅依赖于介质中表面活性剂的增溶作用。此外,除了固体石蜡外,储存还会影响挤出物表面的外观和所有脂质的溶解速率。