Department of Pharmaceutical Technology, Hacettepe University, Ankara, Turkey.
Department of Pharmaceutical Technology, Ataturk University, Erzurum, Turkey.
Pharm Dev Technol. 2020 Oct;25(8):999-1009. doi: 10.1080/10837450.2020.1772290. Epub 2020 Jun 11.
Diabetes is characterized by chronic hyperglycemia. Although metformin hydrochloride (MHCl)- and glyburide (GLB)-containing conventional tablets are available in the market and used to treat diabetes, orally disintegrating tablets (ODTs) containing the combination of these drugs are not commercially available. Therefore, the aim of this study was to prepare ODTs containing MHCl and GLB by direct-compression (DC-ODTs) and freeze-drying (FD-ODTs) methods. Physical properties of the powder mixture of DC-ODT formulation were determined (Angle of repose: 37.18 ± 1.27°; compressibility index: 20.31 ± 1.06%; Hausner ratio: 1.25 ± 0.03). Its moisture content was 0.3 ± 0.09%. The hardness values and the disintegration times for DC-ODTs and FD-ODTs were 221.60 ± 40.82 and 66.54 ± 2.68 N, and 80 and 30 s, respectively. Friability values were 0.24% for DC-ODTs and 0.38% for FD-ODTs. In uniformity-of-mass for single-dose-preparations test, the average weight was 684.38 ± 1.97 mg for DC-ODTs and 342.93 ± 2.4 mg for FD-ODTs, with less than 5% deviation for all 20 tablets. Water-absorption ratio for DC-ODTs was 1.30 ± 0.05. More than 90% of MHCl and GLB were dissolved within 5 min in both DC-ODTs and FD-ODTs. Although Caco-2 permeability of MHCl was influenced by the ODTs, GLB permeability was not. These results indicated that MHCl- and GLB-containing ODTs may be used as promising formulations for the treatment of diabetes.
糖尿病的特征是慢性高血糖。虽然市场上有含有盐酸二甲双胍（MHCl）和格列本脲（GLB）的常规片剂，并且用于治疗糖尿病，但含有这些药物的口服分散片（ODT）尚未商业化。因此，本研究旨在通过直接压片（DC-ODT）和冷冻干燥（FD-ODT）方法制备含有 MHCl 和 GLB 的 ODT。测定了 DC-ODT 配方粉末混合物的物理性质（休止角：37.18±1.27°；可压缩性指数：20.31±1.06%；Hausner 比：1.25±0.03）。其水分含量为 0.3±0.09%。DC-ODT 和 FD-ODT 的硬度值和崩解时间分别为 221.60±40.82 和 66.54±2.68 N 和 80 和 30 s。DC-ODT 的脆碎度值为 0.24%，FD-ODT 的脆碎度值为 0.38%。在单剂量制剂测试的均匀度-质量测试中，DC-ODT 的平均重量为 684.38±1.97 mg，FD-ODT 的平均重量为 342.93±2.4 mg，所有 20 片的偏差均小于 5%。DC-ODT 的吸水率为 1.30±0.05。在 DC-ODT 和 FD-ODT 中，MHCl 和 GLB 均在 5 分钟内溶解超过 90%。虽然 MHCl 的 Caco-2 渗透性受到 ODT 的影响，但 GLB 的渗透性不受影响。这些结果表明，含有 MHCl 和 GLB 的 ODT 可能是治疗糖尿病的有前途的制剂。
