Abstract：
Bedaquiline (BQ) solid lipid nanoparticles (SLNs), which have previously been formulated for parenteral administration, have a risk of patient non-compliance in treating tuberculosis. This research presents a strategy to develop BQ SLNs for oral delivery to improve patient adherence, The upper and lower levels for the formulation excipients were generated from screening experiments. Using 4 input factors (BQ, lecithin, Tween 80, and PEG), a full factorial design from 3 × 2x2 × 2 experiments was randomly arranged to investigate 3 response variables: Particle size distribution (PSD), polydispersity index (PdI), and zeta potential (ZP). High shear homogenization was used to mix the solvent and aqueous phases, with 15% sucrose as a cryoprotectant. The response variables were assessed using a zeta sizer while TEM micrographs confirmed the PSD data. Solid-state assessments were conducted using powdered X-ray diffraction and scanning electron microscopy (SEM) imaging. A comparative invitro assessment was used to determine drug release from an equivalent dose of BQ free base powder and BQ-SLN, both packed in hard gelatin capsules. The sonicated formulations obtained significant effects for PSD, PdI, and ZP. The p-values (0.0001 for PdI, 0.0091 for PSD) for BQ as an independent variable in the sonicated formulation were notably higher than those in the unsonicated formulation (0.1336 for PdI, 0.0117 for PSD). The SEM images were between 100 - 400 nm and delineated nanocrystals of BQ embedded in the lipid matrix. The SLN formulation provides higher drug levels over the drug\'s free base; a similarity factor (f2 = 18.3) was estimated from the dissolution profiles.
摘要：
Bedaquiline（BQ）固体脂质纳米粒（SLN），以前已经配制用于肠胃外给药，有患者不遵守结核病治疗的风险。这项研究提出了一种策略来开发BQSLN口服给药，以提高患者的依从性。制剂赋形剂的上限和下限水平由筛选实验产生。使用4个输入因子(BQ，卵磷脂,吐温80和PEG)，来自3×2x2×2实验的全因子设计随机排列以研究3个响应变量：粒度分布（PSD），多分散指数(PdI)，和zeta电位(ZP)。高剪切均化用于混合溶剂和水相，15％蔗糖作为冷冻保护剂。使用ζ分析仪评估响应变量,而TEM显微照片证实PSD数据。使用粉末X射线衍射和扫描电子显微镜（SEM）成像进行固态评估。使用对比的体外评估来确定等效剂量的BQ游离基粉和BQ-SLN的药物释放，两者都包装在硬明胶胶囊中。超声处理的制剂对PSD获得了显著的影响，PdI,ZP。p值(PdI为0.0001，在超声处理的配方中，作为自变量的BQ为0.0091）明显高于未超声处理的配方（PdI为0.1336，0.0117用于PSD)。SEM图像在100-400nm之间,描绘了嵌入脂质基质中的BQ纳米晶体。与药物的游离碱相比,SLN制剂提供更高的药物水平;从溶出曲线估计相似因子(f2=18.3)。
