维生素A棕榈酸酯传递体处方及工艺优化

Optimization of Formulation and Process for Vitamin A Palmitate Transfersomes

以粒径、ζ电位为考察指标,采用单因素法考察剪切速度、乙醇溶液滴加速度及高压均质次数等工艺因素,以及磷脂种类、表面活性剂、电解质及投药量等处方因素对维生素A棕榈酸酯(1)传递体的影响,并初步评价了传递体的稳定性。所得最佳处方与工艺为:取大豆磷脂1 g、Tween-80 0.2 g和1 0.2 g,溶于无水乙醇0.5 ml中;另取苯氧乙醇0.5 g溶于水约100 ml中。水相保持13 000 r/min的剪切速度,以2 ml/min速度滴加乙醇溶液,得初级传递体,然后在1 500 bar压力下均质1次得纳米传递体。优化后产品的平均粒径为(100.8±16.5)nm,ζ电位为(-43.7±1.1)mV,包封率为(96.2±1.2)%,但该传递体在4℃贮存6个月粒径和药物含量下降,ζ电位绝对值增大。

The effects of process influence factors （shearing speed, adding speed of ethanol solution and homogeneous times） and formulation influence factors （the types of phospholipids, amounts of surfactants, electrolyte and drug） on the quality of vitamin A palmitate （1） transfersomes were investigated with particle size and ζ potential as the indexes by single factor tests. The preliminary stability of the product was also tested. The optimal preparation was as follows： dissolving phospholipids （1 g）, Tween-80 （0.2 g） and 1 （0.2 g） into 0.5 ml of ethanol as oil phase, dissolving phenoxyethanol （0.5 g） into 100 ml of water as water phase, dropping the oil phase with 2 ml/min into the water phase kept the shearing speed of 13 000 r/min to obtain the primary transfersomes, then high pressure homogenization under the pressure of 1 500 bar for one times to obtain the final product. The particle size, ζ potential and entrapment efficiency of the optimized product were （100.8±16.5）nm, （-43.7±1.1）mV and （96.2±1.2）%, respectively. However, when the product was stored at 4 ℃ for 6 months, the particle size and drug content were decreased while the absolute value of ζ potential was increased.