Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey.
Int J Pharm. 2022 Jan 5;611:121294. doi: 10.1016/j.ijpharm.2021.121294. Epub 2021 Nov 15.
Carvedilol (CAR) is a widely studied, beta and alpha-1 blocker, antihypertensive drug due to its poor water solubility and low oral bioavailability (25-35%). The aim of this work is to improve poor water solubility and the pharmacokinetic parameters of carvedilol by using an optimized and self-assembly prepared micelle formulation. Optimized micelle formulation composed of Pluronic® F127, D-α-tocopheryl polyethylene glycol 1000 succinate, L-cysteine HCl in a ratio of 4:3:3. Micellar size, polydispersity index, zeta potential, morphology, critical micelle concentration, thermal behaviors, in-vitro dissolution of micelles and pharmacokinetic parameters in rats were characterized in this study. Carvedilol aqueous solubility increased (up to 271-fold) as a result of its encapsulation within a mixed micelle formulation. The measured micellar sizes of blank and carvedilol loaded mixed micelles are lower than 30 nm with size distributions of 26.69 ± 2.93 nm and 24.16 ± 4.89 nm, respectively. Transmission electron microscopy revealed that the micelles were spherically shaped. There is a significant enhancement of carvedilol dissolution compared to commercially available tablet formulation (f2 < 50). The in-vivo test demonstrated that the t and AUC values of micelles were approximately 10.89- and 2.65-fold greater than that of the commercial tablets, respectively. Based on our study, bring such applications into being may provide effective new drugs for treatment armamentarium of cardiovascular diseases and hypertension in near future.
卡维地洛（CAR）是一种广泛研究的β和α-1 阻滞剂，抗高血压药物，由于其水溶性差和口服生物利用度低（25-35%）。本工作旨在通过使用优化的自组装胶束制剂来改善卡维地洛的水溶性差和药代动力学参数。优化的胶束制剂由 Pluronic® F127、D-α-生育酚聚乙二醇 1000 琥珀酸酯、L-半胱氨酸盐酸盐以 4:3:3 的比例组成。在这项研究中，对胶束的粒径、多分散指数、Zeta 电位、形态、临界胶束浓度、热行为、胶束体外溶解和大鼠药代动力学参数进行了表征。卡维地洛的水溶解度因包封在混合胶束制剂中而增加（高达 271 倍）。空白和载药混合胶束的测量胶束粒径均低于 30nm，分别为 26.69±2.93nm 和 24.16±4.89nm。透射电子显微镜显示胶束呈球形。与市售片剂制剂相比，卡维地洛的溶解有显著提高（f2<50）。体内试验表明，胶束的 t 和 AUC 值分别约为市售片剂的 10.89 倍和 2.65 倍。基于我们的研究，将此类应用变为现实可能为心血管疾病和高血压的治疗手段提供有效的新药，在不久的将来。
