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通过行星球磨法制备盐酸吡格列酮纳米粒子的共稳定化作用: 及评价。

Co-stabilization of pioglitazone HCL nanoparticles prepared by planetary ball milling: and evaluation.

机构信息

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Al-Azhar University, Assiut, Egypt.

出版信息

Pharm Dev Technol. 2020 Sep;25(7):845-854. doi: 10.1080/10837450.2020.1744163. Epub 2020 Mar 23.

Abstract

Pioglitazone (PGZ) is an oral antidiabetic agent that increases cell resistance to insulin, thereby decreasing blood glucose levels. PGZ is a class II drug. Because of its pH-dependent solubility, it precipitates at the intestinal pH, resulting in an erratic and incomplete absorption following oral administration, which causes fluctuations in its plasma concentration. A nanoparticle drug delivery system offers a solution to enhance the dissolution rate of this poorly water-soluble drug. PGZ nanoparticles were formulated by the wet milling technique using a planetary ball mill. The effects of the steric stabilizer (Pluronic F-127, PL F-127), electrostatic stabilizer (sodium deoxycholate, SDC), and number of milling cycles were optimized using a Box-Behnken factorial design. The results showed that the ratio of PL F-127: SDC significantly affected the zeta potential and the dissolution efficiency (DE%) of PGZ. The optimized PGZ nanoparticle formulation enhanced the dissolution to reach 100% after 5 min. The results showed significant enhancement in C (1.3-fold) compared to that of the raw powder, and both AUC and AUC were significantly ( < 0.05) enhanced. In conclusion, PGZ nanoparticle formulation had enhanced dissolution rate in the alkaline media, which improved its drug bioavailability relative to that of the untreated drug.

摘要

吡格列酮(PGZ)是一种口服抗糖尿病药物,可增加细胞对胰岛素的抵抗力,从而降低血糖水平。PGZ 是一种 II 类药物。由于其 pH 依赖性溶解度,它在肠道 pH 下沉淀,导致口服后吸收不规则和不完全,从而导致其血浆浓度波动。纳米药物递送系统提供了一种解决方案,可以提高这种水溶性差的药物的溶解速率。使用行星球磨机通过湿磨技术制备 PGZ 纳米颗粒。使用 Box-Behnken 析因设计优化了空间稳定剂(Pluronic F-127,PL F-127)、静电稳定剂(脱氧胆酸钠,SDC)和研磨循环次数的影响。结果表明,PL F-127:SDC 的比例显著影响 PGZ 的zeta 电位和溶解效率(DE%)。优化的 PGZ 纳米颗粒制剂可增强溶解作用,在 5 分钟后达到 100%。结果表明,与原药相比,C 显著增加(增加 1.3 倍),AUC 和 AUC 均显著增加(<0.05)。总之,PGZ 纳米颗粒制剂在碱性介质中具有增强的溶解速率,相对于未处理的药物提高了其药物生物利用度。

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