Molpeceres J, Aberturas M R, Chacón M, Berges L, Guzmán M
Dpto Farmacia y Tecnología Farmacéutica, Universidad de Alcalá, Alcalá de Henares (Madrid), Spain.
J Microencapsul. 1997 Nov-Dec;14(6):777-87. doi: 10.3109/02652049709006828.
The aim was to evaluate the long-term stability of cyclosporin A-loaded nanoparticle suspensions, stored at 8 and 25 degrees C. The stability of freeze-dried samples was also investigated. Nanoparticles (NP) of poly-sigma-caprolactone (P sigma CL), a biodegradable polymer, were obtained by a modified nanoprecipitation method. A central composite experimental design was used to investigate the simultaneous effect of technological factors (temperature of the aqueous phase and needle gauge) and formulation variables (volume of acetone and the amount of polymer and surfactant). The effect of these variables on the stability of the 100-220 nm particles obtained was evaluated. The percentage of cyclosporin A (CyA) encapsulated in the NP suspensions stored at 8 and 25 degrees C for at least 3 months remained unaltered. Moreover, there was no change in the size of NP. After 4 months storage, the physical stability of the preparation was affected. NP aggregates could be observed by light microscopy. Reconstituted freeze-dried preparations showed a mean increase of 1% in the incorporated drug and also a considerable increase in mean size and size distribution. Additional experiments investigated the effect of freezing temperature (-70 and -196 degrees C) and of 5, 10 and 20% (w/v) cryoprotector (mannitol, sorbitol, glucose and threalose) on 100 nm particles. The addition of glucose and threalose at concentrations > 10% permitted adequate reconstitution of the freeze-dried product with conservation of the encapsulated CyA.
目的是评估负载环孢素A的纳米颗粒悬浮液在8摄氏度和25摄氏度下储存的长期稳定性。还研究了冻干样品的稳定性。通过改进的纳米沉淀法获得了可生物降解聚合物聚-σ-己内酯（PσCL）的纳米颗粒（NP）。采用中心复合实验设计来研究工艺因素（水相温度和针规）和配方变量（丙酮体积、聚合物和表面活性剂用量）的同时作用。评估了这些变量对所获得的100 - 220纳米颗粒稳定性的影响。在8摄氏度和25摄氏度下储存至少3个月的NP悬浮液中包封的环孢素A（CyA）百分比保持不变。此外，NP的大小没有变化。储存4个月后，制剂的物理稳定性受到影响。通过光学显微镜可观察到NP聚集体。重构的冻干制剂显示掺入药物平均增加1%，并且平均大小和大小分布也有相当大的增加。额外的实验研究了冷冻温度（-70摄氏度和-196摄氏度）以及5%、10%和20%（w/v）的冷冻保护剂（甘露醇、山梨醇、葡萄糖和海藻糖）对100纳米颗粒的影响。浓度>10%的葡萄糖和海藻糖的添加使得冻干产品能够充分重构，同时保留包封的CyA。
