Department of Pharmaceutical Technology, Medical University of Gdańsk, M. Skłodowskiej-Curie 3a Street, 80-210, Gdańsk, Poland.
Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06123, Perugia, Italy.
AAPS PharmSciTech. 2019 Jan 2;20(1):19. doi: 10.1208/s12249-018-1203-0.
To take advantage of solid-state properties, the nano spray-drying (NSD) technique was investigated as an innovative one-step method to produce solid lipid nanoparticles (SLN) in the form of a dry powder starting from a lipid/leucine O/W emulsion. Compritol was chosen as wall-forming lipid. Rapamycin (Rp) was employed as a model drug to be loaded into SLN. Based on an initial screening, Lutrol F68 was chosen as surfactant and high-shear homogenization as an emulsification method. A two-level fractional factorial design and an extended factorial design were employed to determine critical factors and best preparation conditions. Compritol concentration, L-leucine/lipid ratio, and Lutrol F68 concentration resulted critical. Best conditions granted 51% yield, 3.2 μm L-leucine/SLN particle size, and a SLN population around 150 nm. All samples showed the presence of lipid aggregates. Material loss in the emulsification step was found responsible for SLN aggregation and low yield. The almost quantitative Rp loading increased SLN population span. Replacing compritol with cetyl palmitate produced aggregation of dry powders and SLN. Overall, NSD was found a fast method to produce SLN dry powders. More insightful assessment of the emulsification step and lipid property effects will be critical to the optimization of the NSD process. Hypotheses account for direct coupling of high-pressure homogenization with NSD for future successful development of this promising manufacturing method.
为了利用固态特性，研究了纳米喷雾干燥（NSD）技术，将其作为一种创新的一步法，从脂质/亮氨酸 O/W 乳液开始生产固态脂质纳米粒（SLN）干粉的形式。选用 Compritol 作为壁形成脂质。将雷帕霉素（Rp）用作载药模型，负载到 SLN 中。基于初步筛选，选择 Lutrol F68 作为表面活性剂，高剪切匀化作为乳化方法。采用两水平分因子设计和扩展因子设计来确定关键因素和最佳制备条件。Compritol 浓度、L-亮氨酸/脂质比和 Lutrol F68 浓度是关键因素。最佳条件可获得 51%的产率、3.2μm 的 L-亮氨酸/SLN 粒径和 150nm 左右的 SLN 群体。所有样品均显示存在脂质聚集体。乳化步骤中的材料损失被认为是导致 SLN 聚集和产率低的原因。几乎定量的 Rp 负载增加了 SLN 群体跨度。用十六烷醇棕榈酸酯替代 Compritol 会导致干粉和 SLN 的聚集。总体而言，NSD 是一种生产 SLN 干粉的快速方法。对乳化步骤和脂质性质影响的更深入评估对于优化 NSD 工艺至关重要。假设将高压匀化与 NSD 直接耦合，为未来成功开发这种有前途的制造方法提供了依据。
