Department of Pharmaceutical Sciences and Technology (Deemed University), Institute of Chemical Technology, N.P. Marg, Matunga (E), Mumbai 400019, Maharastra, India.
AAPS PharmSciTech. 2010 Mar;11(1):304-13. doi: 10.1208/s12249-010-9382-3. Epub 2010 Feb 25.
The present study evaluates freeze thaw as a simple approach for screening the most appropriate cryoprotectant. Freeze-thaw study is based on the principle that an excipient, which protects nanoparticles during the first step of freezing, is likely to be an effective cryoprotectant. Nanoparticles of rifampicin with high entrapment efficiency were prepared by the emulsion-solvent diffusion method using dioctyl sodium sulfosuccinate (AOT) as complexing agent and Gantrez AN-119 as polymer. Freeze-thaw study was carried out using trehalose and fructose as cryoprotectants. The concentration of cryoprotectant, concentration of nanoparticles in the dispersion, and the freezing temperature were varied during the freeze-thaw study. Cryoprotection increased with increase in cryoprotectant concentration. Further, trehalose was superior to fructose at equivalent concentrations and moreover permitted use of more concentrated nanosuspensions for freeze drying. Freezing temperature did not influence the freeze-thaw study. Freeze-dried nanoparticles revealed good redispersibility with a size increase that correlated well with the freeze-thaw study at 20% w/v trehalose and fructose. Transmission electron microscopy revealed round particles with a size approximately 400 nm, which correlated with photon correlation spectroscopic measurements. Differential scanning calorimetry and X-ray diffraction suggested amorphization of rifampicin. Fourier transfer infrared spectroscopy could not confirm interaction of drug with AOT. Nanoparticles exhibited sustained release of rifampicin, which followed diffusion kinetics. Nanoparticles of rifampicin were found to be stable for 12 months. The good correlation between freeze thaw and freeze drying suggests freeze-thaw study as a simple and quick approach for screening optimal cryoprotectant for freeze drying.
本研究评估了冻融法作为筛选最合适的冷冻保护剂的一种简单方法。冻融研究基于这样一个原理，即在冷冻的第一步中保护纳米粒子的赋形剂很可能是一种有效的冷冻保护剂。采用乳化-溶剂扩散法，以二辛基磺基琥珀酸钠（AOT）为络合剂，以 Gantrez AN-119 为聚合物，制备了高包封率的利福平纳米粒。使用海藻糖和果糖作为冷冻保护剂进行冻融研究。在冻融研究中，改变了冷冻保护剂的浓度、分散体中纳米粒的浓度和冷冻温度。随着冷冻保护剂浓度的增加，冷冻保护作用增加。此外，在等效浓度下，海藻糖优于果糖，而且允许使用更浓缩的纳米混悬液进行冷冻干燥。冷冻温度不影响冻融研究。冷冻干燥的纳米粒具有良好的再分散性，粒径增加与 20%w/v 海藻糖和果糖的冻融研究相关性良好。透射电子显微镜显示出粒径约为 400nm 的圆形颗粒，与光相关光谱测量结果相符。差示扫描量热法和 X 射线衍射表明利福平无定形化。傅里叶变换红外光谱不能证实药物与 AOT 的相互作用。纳米粒显示出利福平的持续释放，遵循扩散动力学。利福平纳米粒在 12 个月内稳定。冻融研究与冷冻干燥之间的良好相关性表明，冻融研究是筛选冷冻干燥最佳冷冻保护剂的一种简单快速的方法。
