Department of Pharmacognosy, Poznan University of Medical Sciences, 4 Swiecickiego Street, 60-781 Poznan, Poland.
Institute of Materials Science and Engineering, Poznan University of Technology, Jana Pawła II 24, 61-138 Poznan, Poland.
Molecules. 2021 Sep 1;26(17):5318. doi: 10.3390/molecules26175318.
The amorphous form of carvedilol phosphate (CVD) was obtained as a result of grinding. The identity of the obtained amorphous form was confirmed by powder X-ray diffraction (PXRD), different scanning calorimetry (DSC), and FT-IR spectroscopy. The process was optimized in order to obtain the appropriate efficiency and time. The crystalline form of CVD was used as the reference standard. Solid dispersions of crystalline and amorphous CVD forms with hydrophilic polymers (hydroxypropyl-β-cyclodextrin, Pluronic F-127, and Soluplus) were obtained. Their solubility at pH 1.2 and 6.8 was carried out, as well as their permeation through a model system of biological membranes suitable for the gastrointestinal tract (PAMPA-GIT) was established. The influence of selected polymers on CVD properties was defined for the amorphous form regarding the crystalline form of CVD. As a result of grinding (four milling cycles lasting 15 min with 5 min breaks), amorphous CVD was obtained. Its presence was confirmed by the "halo effect" on the diffraction patterns, the disappearance of the peak at 160.5 °C in the thermograms, and the changes in position/disappearance of many characteristic bands on the FT-IR spectra. As a result of changes in the CVD structure, its lower solubility at pH 1.2 and pH 6.8 was noted. While the amorphous dispersions of CVD, especially with Pluronic F-127, achieved better solubility than combinations of crystalline forms with excipients. Using the PAMPA-GIT model, amorphous CVD was assessed as high permeable ( > 1 × 10 cm/s), similarly with its amorphous dispersions with excipients (hydroxypropyl-β-cyclodextrin, Pluronic F-127, and Soluplus), although in their cases, the values of apparent constants permeability were decreased.
通过研磨获得了卡维地洛磷酸盐（CVD）的无定形形式。通过粉末 X 射线衍射（PXRD）、差示扫描量热法（DSC）和傅里叶变换红外光谱（FT-IR）对所获得的无定形形式的身份进行了确认。为了获得适当的效率和时间，对该过程进行了优化。将 CVD 的晶型用作参考标准。获得了亲水聚合物（羟丙基-β-环糊精、泊洛沙姆 F-127 和 Soluplus）的 CVD 晶型和无定形形式的固体分散体。在 pH 值为 1.2 和 6.8 下进行了它们的溶解度测试，并建立了适用于胃肠道的生物膜模型系统（PAMPA-GIT）的渗透测试。与 CVD 的晶型相比，定义了所选聚合物对无定形形式的 CVD 性质的影响。通过研磨（四个持续 15 分钟、每次 5 分钟休息的研磨循环）获得了无定形 CVD。其存在通过衍射图案上的“晕影效应”、热谱中 160.5°C 处峰的消失以及 FT-IR 光谱上许多特征带的位置变化/消失得到确认。由于 CVD 结构的变化，其在 pH 值为 1.2 和 pH 值为 6.8 时的溶解度较低。而 CVD 的无定形分散体，尤其是与泊洛沙姆 F-127 的组合，其溶解度优于与赋形剂的晶型组合。使用 PAMPA-GIT 模型，评估无定形 CVD 具有高渗透性（>1×10cm/s），与赋形剂（羟丙基-β-环糊精、泊洛沙姆 F-127 和 Soluplus）的无定形分散体类似，尽管在这些情况下，表观渗透常数的值降低了。
