■通过热熔挤出(HME)技术制备姜黄素纳米晶体(Cur-NC),以提高姜黄素(Cur)的溶出度和生物利用度。
■以Eudragit®EPO(EEP)为载体,通过一步挤出工艺制备具有不同药物-载体比例的Cur-NC。通过动态光散射(DLS)表征了Cur在挤出样品中的分散尺寸和固态,扫描电子显微镜(SEM),差示扫描量热法(DSC),和X射线衍射(XRD)。通过热重分析(TGA)和高效液相色谱(HPLC)分析Cur的热稳定性。研究了纳米制剂对Cur溶出和吸收的改善作用。
通过使用1:1、2:1和4:1的药物-载体比率成功地制备了粒径在50〜150nm范围内的Cur-NC,并且Cur的晶体形式在HME之前和之后均为形式1。挤出粉末显示出非常有效的溶解,在不到2分钟的时间内累积溶解百分比为80%,它们的固有溶出速率分别为13.68±1.20mg/min/cm2、11.78±0.57mg/min/cm2和4.35±0.20mg/min/cm2,而纯Cur的浓度仅为0.04±0.00mg/min/cm2。TGA数据表明Cur的降解温度约为250°C,而HPLC结果显示Cur在超过150°C的温度下挤出时降解。药代动力学实验表明Cur的吸收有明显改善。Cur-NC组的Cmax是单纯Cur组的1.68倍,代谢物的Cmax和曲线下面积(AUC0-∞)分别是纯Cur组的2.79和4.07倍。
■Cur-NC可以通过HME技术一步制备,这显著提高了Cur的溶出度和生物利用度。如许一种制备不溶性药物纳米晶的新办法具有辽阔的运用远景。
UNASSIGNED: Curcumin nanocrystals (Cur-NCs) were prepared by hot melt extrusion (HME) technology to improve the dissolution and bioavailability of curcumin (Cur).
UNASSIGNED: Cur-NCs with different drug-carrier ratios were prepared by one-step extrusion process with Eudragit® EPO (EEP) as the carrier. The dispersed size and solid state of Cur in extruded samples were characterized by dynamic light scattering (DLS), scanning electron microscope (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The thermal stability of Cur was analyzed by thermogravimetric analysis (TGA) and high performance liquid chromatography (HPLC). Dissolution and pharmacokinetics were studied to evaluate the improvement of dissolution and absorption of Cur by nano-preparation.
UNASSIGNED: Cur-NCs with particle sizes in the range of 50~150 nm were successfully prepared by using drug-carrier ratios of 1:1, 2:1 and 4:1, and the crystal form of Cur was Form 1 both before and after HME. The extrudate powders showed very efficient dissolution with the cumulative dissolution percentage of 80% in less than 2 min, and the intrinsic dissolution rates of them were 13.68 ± 1.20 mg/min/cm2, 11.78 ± 0.57 mg/min/cm2 and 4.35 ± 0.20 mg/min/cm2, respectively, whereas that of pure Cur was only 0.04 ± 0.00 mg/min/cm2. The TGA data demonstrated that the degradation temperature of Cur was about 250 °C, while the HPLC results showed Cur was degraded when extruded at the temperature over 150 °C. Pharmacokinetic experiment showed a significant improvement in the absorption of Cur. The Cmax of Cur in the Cur-NC group was 1.68 times that of pure Cur group, and the Cmax and area under the curve (AUC0-∞) of metabolites were 2.79 and 4.07 times compared with pure Cur group.
UNASSIGNED: Cur-NCs can be prepared by HME technology in one step, which significantly improves the dissolution and bioavailability of Cur. Such a novel method for preparing insoluble drug nanocrystals has broad application prospects.