Tran Thuy, Xi Xi, Rades Thomas, Müllertz Anette
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark; Bioneer: FARMA, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Int J Pharm. 2016 Apr 11;502(1-2):151-60. doi: 10.1016/j.ijpharm.2016.02.026. Epub 2016 Feb 22.
The study investigated the use of monoacyl phosphatidylcholine (MAPC) in self-nanoemulsifying drug delivery system (SNEDDS). A D-optimal design was used to generate two sets of formulations containing long-chain (LC) or medium-chain (MC) glycerides, caprylocaproyl macrogol-8 glycerides (Labrasol), Lipoid S LPC 80 (LPC) (80% MAPC) and ethanol. The formulations were characterized using dynamic light scattering, microscopy, in vitro lipolysis and viscometric measurements. All LC formulations within the investigated range were predicted to generate polydisperse emulsions while MC formulations generated nanoemulsions with droplet sizes from 23 to 167 nm. Using LPC in MC formulations reduced the nanoemulsion droplet sizes in simulated gastric and intestinal media. The nanoemulsion droplet size of MC SNEDDS containing LPC was not affected by gastrointestinal pH, while the zeta potentials increased at low pH. During in vitro lipolysis, less fatty acids were released when LPC was incorporated into the formulations (2.05 ± 0.02 mmol reduced to 1.76 ± 0.05 mmol when incorporating 30% LPC). Replacing Labrasol by LPC increased the formulation dynamic viscosity from 57 ± 1 mPas (0% LPC) to 436 ± 8 mPas (35% LPC) at 25°C, however, this did not considerably prolong the formulation dispersion time. In conclusion, MC SNEDDS containing LPC are promising formulations when desiring to reduce the amount of synthetic surfactants and possibly modify the digestion rate.
该研究调查了单酰基磷脂酰胆碱（MAPC）在自纳米乳化药物递送系统（SNEDDS）中的应用。采用D-最优设计来制备两组含有长链（LC）或中链（MC）甘油酯、辛酸癸酸聚乙二醇-8甘油酯（Labrasol）、Lipoid S LPC 80（LPC）（80% MAPC）和乙醇的制剂。通过动态光散射、显微镜检查、体外脂解和粘度测量对制剂进行表征。在所研究的范围内，所有LC制剂预计会产生多分散乳液，而MC制剂产生的纳米乳液液滴尺寸为23至167纳米。在MC制剂中使用LPC可降低模拟胃和肠介质中的纳米乳液液滴尺寸。含有LPC的MC SNEDDS的纳米乳液液滴尺寸不受胃肠道pH值的影响，而ζ电位在低pH值时会增加。在体外脂解过程中，当LPC加入制剂中时，释放的脂肪酸较少（加入30% LPC时，从2.05±0.02毫摩尔降至1.76±0.05毫摩尔）。用LPC替代Labrasol可使制剂在25°C时的动态粘度从57±1毫帕秒（0% LPC）增加到436±8毫帕秒（35% LPC），然而，这并没有显著延长制剂的分散时间。总之，当希望减少合成表面活性剂的用量并可能改变消化速率时，含有LPC的MC SNEDDS是有前景的制剂。
