Haidar Iman, Harding Ian H, Bowater Ian C, Eldridge Daniel S, Charman William N
Faculty of Science I, Department of Chemistry and Biochemistry, Lebanese University, Hadath, Beirut, Lebanon.
Department of Chemistry and Biotechnology, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Melbourne, Australia.
Int J Pharm. 2017 Aug 7;528(1-2):524-535. doi: 10.1016/j.ijpharm.2017.06.040. Epub 2017 Jun 13.
We report on the successful incorporation of the antimalarial drug, halofantrine, into laboratory based soybean oil emulsions which were designed to mimic the commercially available parenteral fat emulsion, Intralipid. A high pH (minimum of pH 9, preferable pH of 11) was required for the drug laden emulsion to remain stable on storage and also to resist breaking under various stresses. Ageing of lecithin samples on storage was noted to result in degradation and a decrease in pH. We argue that this is the main reason for a similar decrease in pH for lecithin based emulsions and subsequent instability in drug laden emulsions. As expected, incorporation of the drug (halofantrine) resulted in lower stability. The (intensity weighted) particle size increased from 281nm for the drug free emulsion to 550nm following a loading of 1gL of halofantrine, indicative of a lowering in stability and this was reflected in a shorter shelf life. Interestingly, incorporation of even higher concentrations of drug then resulted in better stability albeit never as stable as the drug free emulsion. We also report on unusual and complex surface tension behaviour for fresh lecithin where multiple critical concentration points were observed.
我们报告了将抗疟药物卤泛群成功掺入基于实验室的大豆油乳剂中的情况，该乳剂旨在模拟市售的肠外脂肪乳剂英脱利匹特。载药乳剂要在储存时保持稳定并在各种应力下抗破裂，需要高pH值（最低pH 9，优选pH 11）。储存时卵磷脂样品的老化会导致降解和pH值降低。我们认为这是基于卵磷脂的乳剂pH值出现类似降低以及随后载药乳剂不稳定的主要原因。正如预期的那样，药物（卤泛群）的掺入导致稳定性降低。（强度加权）粒径从不含药物的乳剂的281nm增加到加载1g/L卤泛群后的550nm，表明稳定性降低，这反映在保质期缩短上。有趣的是，掺入更高浓度的药物随后会导致更好的稳定性，尽管从未像不含药物的乳剂那样稳定。我们还报告了新鲜卵磷脂不同寻常且复杂的表面张力行为，观察到了多个临界浓度点。
