3种前列地尔新型制剂理化性质对比研究

Comparative study on physicochemical properties of three kinds of novel preparations of alprostadil

目的:系统比较3种前列地尔新型制剂的理化性质,探讨结构组成与稳定性的关系。方法:采用透射电子显微镜和激光散射仪考察3种前列地尔新型制剂的形态、粒径以及p H值、离子强度和血清对其稳定性的影响;采用傅立叶红外光谱和差示量热扫描技术分析制剂的结构组成;采用超滤法测定3种制剂中前列地尔的包封率。结果:脂质乳呈现出较强的膜结构,有清晰膜边界,粒径约为150 nm;脂微球呈现出鹅卵石状结构,粒径约为200 nm;干乳剂经去离子水复溶后,颗粒无明显膜结构,粒径为200 nm。稳定性实验结果表明,在不同离子强度、p H值和血清影响下,制剂的稳定性顺序为:脂质乳>脂微球>干乳剂。在处方组成上,脂质乳与脂微球基本一致,但处方含量不同,而干乳剂在处方组成与含量上,均与前两者有明显差异;3种制剂的包封率分别为(92.06±1.49)%(脂质乳)、(83.08±6.05)%(脂微球)和(81.99±6.90)%(干乳剂)。结论:3种前列地尔新型制剂的结构和理化性质存在异同,脂质乳和脂微球制剂结构和组成相近,与干乳剂明显不同。与脂微球比较,脂质乳具有更好的稳定性和较高的包封率。

Objective： To systematically compare the structures and physicochemical properties of three kinds of novel preparations of alprostadil, including lipid emulsion （ LE）, lipid nanospheres （ LN）, and dry emulsion （DE）. Methods： Morphological characteristics was observed under transmission electron microscope （TEM）, size distribution and poly-dispersity index （PDI） were determined with laser dynamic scattering instrument, and the effects of pH, ion strength and serum on the stabilities of the three preparations were studied. The structures and components were determined with FT-IR spectrum and differential scanning calorimetry （DSC） technique. The entrapment efficiency （ee%） of alprostadil in the three preparations were determined by super-fihration method. Results： LE had membrane structure and clear membrane boundary, and the particle size was around 150 nm. LN presented the pebble shape structure with particle size of 200 nm. The re-dissolution of DE were granular without membrane structure. Under the influences of different ionic strengths, pH values and serum, the stability of the preparations was as follows： LE 〉 LN 〉 DE. The formulation composition of LE was similar to that of LN, but the content was different. However, DE was obviously different from LE and LN. The entrapment efficiencies of LE, LN and DE were （92.06 ± 1.49） % , （83.08 ± 6.05 ） % , （ 81.99 ± 6.90） % , respectively. Conclusion ： There are similarities and differences in the structures and physicochemical properties among the three kinds of novel alprostadil preparations. LE and LN, which have similar structures, are significantly different from DE. Compared with LN, LE possesses better stability and higher encapsulation efficiency.