College of Pharmacy, Zhejiang University of Technology, Hangzhou, People's Republic of China.
Department of Pharmacy, The 903rd Hospital of People's Liberation Army, Hangzhou, People's Republic of China.
Int J Nanomedicine. 2024 Jun 12;19:5721-5737. doi: 10.2147/IJN.S463918. eCollection 2024.
Curcumin nanocrystals (Cur-NCs) were prepared by hot melt extrusion (HME) technology to improve the dissolution and bioavailability of curcumin (Cur).
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.
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/cm, 11.78 ± 0.57 mg/min/cm and 4.35 ± 0.20 mg/min/cm, respectively, whereas that of pure Cur was only 0.04 ± 0.00 mg/min/cm. 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 C of Cur in the Cur-NC group was 1.68 times that of pure Cur group, and the C and area under the curve (AUC) of metabolites were 2.79 and 4.07 times compared with pure Cur group.
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.
通过热熔挤出（HME）技术制备姜黄素纳米晶体（Cur-NCs），以提高姜黄素（Cur）的溶解度和生物利用度。
采用一步挤出工艺，以 Eudragit EPO（EEP）为载体，制备不同载药比的 Cur-NCs。采用动态光散射（DLS）、扫描电子显微镜（SEM）、差示扫描量热法（DSC）和 X 射线衍射（XRD）对挤出样品中 Cur 的分散粒径和固体状态进行表征。采用热重分析（TGA）和高效液相色谱（HPLC）分析 Cur 的热稳定性。通过溶出度和药代动力学研究来评价纳米制剂对 Cur 溶出度和吸收的改善。
采用载药比为 1:1、2:1 和 4:1，成功制备了粒径为 50~150nm 的 Cur-NCs，且 Cur 的晶体形态在 HME 前后均为 Form 1。挤出物粉末具有非常高效的溶出度，2 分钟内累积溶出率达到 80%，其固有溶出速率分别为 13.68±1.20mg/min/cm、11.78±0.57mg/min/cm 和 4.35±0.20mg/min/cm，而纯 Cur 的固有溶出速率仅为 0.04±0.00mg/min/cm。TGA 数据表明 Cur 的降解温度约为 250°C，而 HPLC 结果表明 Cur 在 150°C 以上挤出时会发生降解。药代动力学实验表明，Cur 的吸收得到显著改善。Cur-NC 组的 CurCmax是纯 Cur 组的 1.68 倍，代谢物的 Cmax和曲线下面积（AUC）分别是纯 Cur 组的 2.79 倍和 4.07 倍。
通过 HME 技术一步法可制备 Cur-NCs，显著提高了 Cur 的溶解度和生物利用度。这种制备难溶性药物纳米晶体的新方法具有广阔的应用前景。
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