Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy and Medical Sciences, Petra University, Amman, Jordan.
AAPS PharmSciTech. 2021 Mar 21;22(3):112. doi: 10.1208/s12249-021-01952-9.
Telmisartan (TLM) is a potent antihypertensive drug with pH-dependent aqueous solubility. This work aimed to enhance the solubility and dissolution rate of TLM by the co-amorphous drug amino acid (AA) approach by combining TLM, with different types and ratios of AAs. The co-amorphous TLM-AA blends were prepared by freeze-drying and investigated for solid-state characteristics like the dissolution rate enhancement of TLM. Among the prepared co-amorphous formulations, TLM-arginine (ARG) exhibited the greatest enhancement in solubility with increasing the molar ratio of ARG. The TLM-ARG at 1:2 ratio showed about a 57-fold increase in solubility of TLM and the highest dissolution percentage in phosphate buffer (pH7.5) (100% in 20 minutes) compared to both crystalline TLM (20% in 60 min) and physical mixture. Powder XRD, DSC, FTIR analysis and SEM demonstrated the formation of amorphous form within the co-amorphous formulations. Only TLM:ARG (1:0.5) were stable at (40°C, 75% RH) for a minimum of 90 days. In conclusion, ARG was able to stabilize the amorphous form of TLM and enhances its aqueous solubility and dissolution. The 1:2 w/w ratio of TLM-ARG co-amorphous showed the best solubility and dissolution rate while the 1:0.5 w/w ratio showed the best stability.
替米沙坦（TLM）是一种具有 pH 依赖性水溶度的强效降压药物。本工作旨在通过共无定形药物氨基酸（AA）方法来提高 TLM 的溶解度和溶解速率，将 TLM 与不同类型和比例的 AA 结合。通过冷冻干燥制备共无定形 TLM-AA 混合物，并对其进行固态特性研究，如 TLM 的溶解速率增强。在所制备的共无定形配方中，TLM-精氨酸（ARG）在增加 ARG 摩尔比时表现出最大的溶解度提高。TLM-ARG 为 1:2 比例时，TLM 的溶解度提高了约 57 倍，在磷酸盐缓冲液（pH7.5）中的溶解百分比最高（20 分钟内为 100%），与结晶 TLM（60 分钟内为 20%）和物理混合物相比。粉末 XRD、DSC、FTIR 分析和 SEM 表明共无定形配方中形成了无定形形式。只有 TLM:ARG（1:0.5）在（40°C，75%RH）下至少 90 天稳定。总之，ARG 能够稳定 TLM 的无定形形式并提高其水溶解度和溶解速率。TLM-ARG 共无定形的 1:2 w/w 比例显示出最佳的溶解度和溶解速率，而 1:0.5 w/w 比例显示出最佳的稳定性。
