Department of Pharmaceutical Technology, University of Bonn, Gerhard-Domagk-Straße 3, 53121, Bonn, Germany.
AbbVie Deutschland GmbH & Co. KG, Knollstraße 50, 67061, Ludwigshafen, Germany.
AAPS PharmSciTech. 2022 May 9;23(5):137. doi: 10.1208/s12249-022-02283-z.
The present study explored vacuum drum drying (VDD) as potential drying technique for the solidification of crystalline ritonavir nanosuspensions prepared by wet-ball milling. In detail, the impact of drying protectants (mannitol, lactose, trehalose) added to the ritonavir nanosuspension was assessed in dependence of the drum temperature with respect to processibility via VDD, resulting intermediate powder properties, remaining nanoparticulate redispersibility and crystallinity. A clear impact of the glass transition temperature (T) of the drying protectant on the redispersibility/crystallinity of the VDD intermediate was observed. Increased T of the drying protectant was associated with improved redispersibility/crystallinity at a defined drum temperature. Consequently, the high T-substance trehalose and lactose showed a better performance than mannitol at higher drum temperatures. However, the processability and related powder properties were not in accordance with this observation. Mannitol containing formulations showed superior processibility to those containing trehalose/lactose. Moreover, the impact of the tableting and encapsulation process on the redispersibility of the VDD intermediate was studied for a selected formulation. Neither process demonstrated a negative impact on redispersibility. In conclusion, vacuum drum drying is a promising drying technique for the solidification of nanosuspensions to result in dried powder still containing ritonavir nanoparticles while demonstrating acceptable to good downstream processibility to tablets/capsules.
本研究探索了真空滚筒干燥（VDD）作为通过湿磨法制备的结晶利托那韦纳米混悬剂固化的潜在干燥技术。详细地说，评估了在 VDD 过程中添加到利托那韦纳米混悬剂中的干燥保护剂（甘露醇、乳糖、海藻糖）的影响，这些保护剂取决于滚筒温度，涉及可加工性、中间粉末特性、残留纳米颗粒再分散性和结晶度。干燥保护剂的玻璃化转变温度（T）对 VDD 中间产物的再分散性/结晶度有明显的影响。干燥保护剂的 T 增加与在定义的滚筒温度下改善再分散性/结晶度相关。因此，在较高的滚筒温度下，高 T 物质海藻糖和乳糖的性能优于甘露醇。然而，加工性能和相关的粉末特性与这一观察结果不一致。含有甘露醇的制剂表现出比含有海藻糖/乳糖的制剂更好的加工性能。此外，还研究了选定配方的压片和包衣过程对 VDD 中间产物再分散性的影响。这两种过程均未对再分散性产生负面影响。总之，真空滚筒干燥是一种很有前途的纳米混悬剂固化干燥技术，可以得到含有利托那韦纳米颗粒的干燥粉末，同时表现出可接受至良好的下游压片/胶囊加工性能。
