The unique nanostructured matrix obtained by silica-lipid hybrids (SLHs) is well known to improve the dissolution, absorption, and bioavailability of poorly water-soluble drugs (PWSDs). The aim of this study was to investigate the impact of: (i) drug load: 3–22.7% w/w, (ii) lipid type: medium-chain triglyceride (Captex 300) and mono and diester of caprylic acid (Capmul PG8), and (iii) silica nanostructure: spray dried fumed silica (FS) and mesoporous silica (MPS), on the in vitro dissolution, solubilization, and solid-state stability of the model drug fenofibrate (FEN). Greater FEN crystallinity was detected at higher drug loads and within the MPS formulations. Furthermore, an increased rate and extent of dissolution was achieved by FS formulations when compared to crystalline FEN (5–10-fold), a commercial product; APO-fenofibrate (2.4–4-fold) and corresponding MPS formulations (2–4-fold). Precipitation of FEN during in vitro lipolysis restricted data interpretation, however a synergistic effect between MPS and Captex 300 in enhancing FEN aqueous solubilization was attained. It was concluded that a balance between in vitro performance and drug loading is key, and the optimum drug load was determined to be between 7–16% w/w, which corresponds to (200–400% equilibrium solubility in lipid S_eq). This study provides valuable insight into the impact of key characteristics of SLHs, in constructing optimized solid-state lipid-based formulations for the oral delivery of PWSDs.

中文翻译：

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多孔纳米结构，脂质组成和药物过饱和程度可调节非脂质体在硅脂混合液中的体外溶解。

众所周知，通过二氧化硅-脂质杂种（SLH）获得的独特的纳米结构基质可改善水溶性差的药物（PWSD）的溶解，吸收和生物利用度。这项研究的目的是调查以下因素的影响：（i）载药量：3–22.7％w / w，（ii）脂质类型：中链甘油三酸酯（Captex 300）和辛酸的单和二酯（Capmul PG8），以及（iii）二氧化硅纳米结构：将喷雾干燥的气相二氧化硅（FS）和中孔二氧化硅（MPS）喷涂在模型药物非诺贝特（FEN）的体外溶出度，增溶性和固态稳定性。在较高的药物负载量和MPS配方中检测到较高的FEN结晶度。此外，与商业产品结晶FEN（5-10倍）相比，FS制剂可提高溶出速率和溶解程度。APO非诺贝特（2.4–4倍）和相应的MPS配方（2–4倍）。在体外脂解过程中FEN的沉淀限制了数据的解释，但是MPS和Captex 300之间在增强FEN水溶液增溶方面具有协同作用。w / w，相当于（在脂质S _eq中的200–400％平衡溶解度）。这项研究为SLHs关键特性的影响提供了宝贵的见解，在构建用于口服递送PWSDs的优化的基于固态脂质的配方中。