Laboratory of Pharmaceutical Technology, Department of Pharmacy, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
Hellenic Agricultural Organization Demeter, Plant Breeding and Genetic Resources Institute, Thermi, 57001, Thessaloniki, Greece.
AAPS PharmSciTech. 2019 Jan 11;20(2):78. doi: 10.1208/s12249-018-1274-y.
Poor aqueous solubility and low bioavailability are limiting factors in the oral delivery of lipophilic drugs. In a formulation approach to overcome these limitations, rice bran (RB) oil was evaluated as drug carrier in the development of self-nanoemulsifying drug delivery systems (SNEDDS). The performance of RB in formulations incorporating Kolliphor RH40 or Kolliphor EL as surfactants and Transcutol HP as cosolvent was compared to a common oil vehicle, corn oil (CO). Serial dilutions of the preconcentrates were performed in various media [distilled water and simulated intestinal fluids mimicking fasted state (FaSSIF) and fed state (FeSSIF)] and at different dilution ratios to simulate the in vivo droplets' behavior. The developed SNEDDS were assessed by means of phase separation, droplet size, polydispersity index, and ζ-potential. Complex ternary diagrams were constructed to identify compositions exhibiting monophasic behavior, droplet size < 100 nm, and polydispersity index (PDI) < 0.25. Multifactor analysis and response surface areas intended to determine the factors significantly affecting droplet size. The oil capacity to accommodate lipophilic drugs was assessed via fluorescence spectroscopy based on the solvatochromic behavior of Nile Red. Solubility studies were performed to prepare fenofibrate- and itraconazole-loaded SNEDDS and assess their droplet size, whereas dissolution experiments were conducted in simulated intestinal fluids. Caco-2 cell viability studies confirmed the safety of the SNEDDS formulations at 1:100 and 1:1000 dilutions after cell exposure in culture for 4 h. The obtained results showed similar performance between RB and CO supporting the potential of RB as oil vehicle for the effective oral delivery of lipophilic compounds.
疏水性药物的口服递送受到其较差的水溶性和低生物利用度的限制。在克服这些限制的制剂方法中，米糠（RB）油被评估为药物载体，用于开发自微乳给药系统（SNEDDS）。与常用油载体玉米油（CO）相比，RB 在含有 Kolliphor RH40 或 Kolliphor EL 作为表面活性剂和 Transcutol HP 作为助溶剂的配方中的性能。对预浓缩物在不同介质（蒸馏水和模拟空腹状态（FaSSIF）和进食状态（FeSSIF）的模拟肠液）和不同稀释比下进行连续稀释，以模拟体内液滴的行为。通过相分离、液滴大小、多分散指数和 ζ-电位来评估所开发的 SNEDDS。构建复杂的三元相图以识别表现出单相行为、液滴大小 < 100nm 和多分散指数（PDI）< 0.25 的组合物。多因素分析和响应面旨在确定显著影响液滴大小的因素。通过基于尼罗红的溶剂化显色行为的荧光光谱法评估油容纳亲脂性药物的能力。进行溶解度研究以制备载有非诺贝特和伊曲康唑的 SNEDDS 并评估其液滴大小，而在模拟肠液中进行溶解实验。Caco-2 细胞活力研究证实，在细胞培养 4 小时后，以 1:100 和 1:1000 的稀释度暴露于 SNEDDS 制剂时，细胞安全性良好。获得的结果表明 RB 和 CO 之间的性能相似，支持 RB 作为油载体用于有效口服递亲水化合物的潜力。
