The purpose of this study was to improve the aqueous solubility and oral bioavailability of practically water-insoluble carvedilol using pH-modulating drug delivery systems. Since carvedilol is weakly basic, its aqueous solubility increases when the drug is surrounded by an acidic microenvironment. Two different microspheres with acidic microenvironment, solvent-evaporated (ASE) and surface-attached (ASA) systems, were prepared in this study using ethanol and distilled water as solvents, respectively. Tartaric acid was selected as the acidifier due to high solubility and excellent compatibility with the drug. ASE microspheres and ASA microspheres were composed of drug/Kollidon® VA64/Tween® 80/tartaric acid at a weight ratio of 1/10/0.5/1 and 1/0.7/0.3/1, respectively. The physicochemical properties of ASE microspheres were consistent; however, ASA microspheres exhibited distinct DSC thermogram and PXRD pattern related to their respective conventional systems. These results can be attributed to partial dissolution of the drug in ASA microspheres due to its pH-dependent solubility behaviour. Both microspheres significantly increased the drug solubility by 5319-fold and 331-fold, respectively, compared to the drug itself (p < 0.05). Moreover, the dissolution rate and oral bioavailability of both formulations was significantly higher than that of the drug (p < 0.05), with ASE being superior to ASA microspheres. Therefore, ASE system is suggested as an optimised pH-modulating drug delivery system for practically water-insoluble carvedilol.

本研究的目的是使用调节 pH 的药物递送系统提高几乎不溶于水的卡维地洛的水溶性和口服生物利用度。由于卡维地洛是弱碱性，当药物被酸性微环境包围时，其水溶性增加。在本研究中，分别使用乙醇和蒸馏水作为溶剂，制备了两种不同的具有酸性微环境的微球，溶剂蒸发 (ASE) 和表面附着 (ASA) 系统。酒石酸因其溶解度高、与药物的相容性好而被选作酸化剂。ASE 微球和 ASA 微球由药物/Kollidon® VA64/Tween® 80/酒石酸组成，重量比分别为 1/10/0.5/1 和 1/0.7/0.3/1。ASE微球的理化性质一致；然而，ASA 微球表现出与它们各自的常规系统相关的不同的 DSC 热谱图和 PXRD 图案。这些结果可归因于药物在 ASA 微球中的部分溶解，这是由于其 pH 依赖性溶解行为。与药物本身相比，两种微球的药物溶解度分别显着提高了 5319 倍和 331 倍。p  < 0.05)。此外，两种制剂的溶出度和口服生物利用度均显着高于药物（p  < 0.05），其中ASE优于ASA微球。因此，建议将 ASE 系统作为一种优化的 pH 调节药物递送系统，用于实际不溶于水的卡维地洛。