穿心莲内酯过饱和自微乳化释药系统的制备及体外评价

目的:优选穿心莲内酯过饱和自微乳化释药系统的处方工艺,以提高穿心莲内酯的溶解度及生物利用度。方法:通过溶解度试验及伪三元相图的工艺初步筛选后,采用单纯形网格法,以粒径、多分散指数和乳化时间为指标,确定穿心莲内酯自微乳的处方;以析晶情况、粒径、多分散指数、乳化时间以及穿心莲内酯的溶出度为考察指标筛选最佳促过饱和抑制剂。结果:穿心莲内酯过饱和自微乳处方为油酸乙酯-(聚山梨酯-80)-聚乙二醇400-羟丙基甲基纤维素K4M(20∶35∶45∶1)。穿心莲过饱和自微乳乳化后的平均粒径(29.26±0.56)nm,多分散指数0.19±0.02,Zeta电位(-10.23±2.34)mV,乳化时间(62.39±2.03)s,1 h累积溶出度高达91%。结论:加入羟丙基甲基纤维素K4M后可明显抑制穿心莲内酯自微乳液的析晶时间,增加自微乳的稳定性;相较于普通自微乳可明显提高穿心莲内酯的体外溶出度,进而提高该成分的生物利用度。

Preparation and in Vitro Evaluation of Andrographolide Supersaturatable Self-microemulsifying Drug Delivery System

Objective: To prepare supersaturatable self-microemulsifying drug delivery system of andrographolide for increasing its solubility and bioavailability. Method: Based on results of solubility test and pseudo-ternary phase diagrams, the formulation of self-microemulsifying drug delivery system was optimized by simplex lattice method with degree of average particle size, polydispersity index and emulsifying time as indexes;and the best supersaturated inhibitor was screened out by means of crystallization, particle size, polydispersity index, self-emulsifying time and dissolution rate of andrographolide. Result: The optimum formulation of andrographolide supersaturated self-microemulsion was ethyl oleate, polysorbate-80, polyethylene glycol 400 and hydroxypropyl methylcellulose K4M in the ration of 20:35:45:1.After emulsification, average particle size, polydispersity index, Zeta potential, emulsifying time and the cumulative dissolution rate at 1 hour of andrographolide supersaturatable drug delivery system were (29.26±0.56) nm, 0.19±0.02, (-10.23±2.34) mV, (62.39±2.03) s and 91%, respectively. Conclusion: The hydroxypropyl methylcellulose K4M can obviously inhibit the crystallization time and increase the stability of the self-microemulsion;compared with the ordinary self-microemulsion, supersaturated self-microemulsion can improve the dissolution of andrographolide obviously, and the bioavailability of andrographolide is improved.