Department of Chemical Engineering and Materials Science, Chung-Ang University, 221, Heukseok-dong, Dongjak-gu, Seoul 156-756, South Korea.
J Pharm Sci. 2009 Dec;98(12):4808-17. doi: 10.1002/jps.21786.
Drug nanoparticles are often prepared in a liquid medium, and a drying method such as freeze drying is used to convert them to an oral solid dosage form. When the dried form is reconstituted in an aqueous system, it may be redispersed to achieve its original particle size. The redispersibility of dried nanoparticles depends on the parameters of the freeze drying process. In this study, an apparatus with a freezing rate gradient was used to systematically investigate the effect of cryoprotectants on the redispersibility of nanoparticles as a function of freezing rate. Sucrose, lactose, mannitol, and polyethylene glycol were used as cryoprotectants for a naproxen nano-suspension. A fast freezing rate and a high cryoprotectant concentration were generally favored. However, under certain conditions, a slower freezing rate resulted in better redispersibility. This is probably because slow freezing can produce a more cryo-concentrated liquid phase, and the concentrated cryoprotectant in the liquid phase can more effectively protect the nanoparticles. An irreversible aggregation map was constructed as a function of the freezing rate and the cryoprotectant concentration, and shows both the favorable and unfavorable effects of cryoprotectants.
药物纳米颗粒通常在液体介质中制备，并使用干燥方法（如冷冻干燥）将其转化为口服固体剂型。当干燥形式在水系统中重新分散时，它可能会重新分散以达到其原始粒径。干燥纳米颗粒的再分散性取决于冷冻干燥过程的参数。在这项研究中，使用具有冷冻速率梯度的设备系统地研究了冷冻保护剂对纳米颗粒再分散性的影响，作为冷冻速率的函数。蔗糖、乳糖、甘露醇和聚乙二醇被用作萘普生纳米混悬剂的冷冻保护剂。通常，快速冷冻速率和高冷冻保护剂浓度是有利的。然而，在某些条件下，较慢的冷冻速率会导致更好的再分散性。这可能是因为缓慢的冷冻可以产生更冷冻浓缩的液相，而液相中的浓缩冷冻保护剂可以更有效地保护纳米颗粒。作为冷冻速率和冷冻保护剂浓度的函数，构建了不可逆聚集图，显示了冷冻保护剂的有利和不利影响。
