Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan.
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan.
Int J Pharm. 2020 Sep 25;587:119637. doi: 10.1016/j.ijpharm.2020.119637. Epub 2020 Jul 12.
To improve the bioavailability of orally-administered drug, solubilization of poorly water-soluble drug is important. The solubility of a drug in its amorphous form is known to be higher than in its crystalline form. In this study, we attempted to adsorb a sublimable drug onto porous calcium silicate (Florite®, FLR) or non-porous calcium silicate (NPCS) by the sealed heating (SH) method and evaporated (EV) method. Ibuprofen (IBU) was used as the poorly water-soluble, sublimable drug. The physicochemical properties of samples were investigated using powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), and dissolution test. From the PXRD and DSC results, IBU crystals were adsorbed and amorphized by the SH and EV methods with FLR. From the results of FTIR, the shift to a higher frequency by the carbonyl stretching vibration band of IBU suggests an intermolecular interaction between IBU and FLR. In SH with FLR, improved solubilization was observed. IBU adsorbed onto FLR showed a greater dissolution rate than the IBU crystals or NPCS. Thus, the petal-like structure of FLR may be an effective method to adsorb IBU onto FLR using the SH method.
为了提高口服药物的生物利用度，提高难溶性药物的溶解度很重要。已知药物的无定形形式的溶解度高于其结晶形式。在这项研究中，我们试图通过密封加热（SH）法和蒸发（EV）法将可升华药物吸附到多孔硅酸钙（Florite®，FLR）或无孔硅酸钙（NPCS）上。布洛芬（IBU）用作难溶性、可升华药物。使用粉末 X 射线衍射（PXRD）、差示扫描量热法（DSC）、傅里叶变换红外光谱（FTIR）和溶解试验研究了样品的物理化学性质。从 PXRD 和 DSC 结果可知，IBU 晶体通过 SH 和 EV 方法与 FLR 吸附并非晶化。从 FTIR 的结果来看，IBU 的羰基伸缩振动带向更高频率的位移表明 IBU 与 FLR 之间存在分子间相互作用。在 SH 中与 FLR 一起，观察到溶解度提高。吸附在 FLR 上的 IBU 显示出比 IBU 晶体或 NPCS 更快的溶解速率。因此，FLR 的花瓣状结构可能是使用 SH 法将 IBU 吸附到 FLR 上的有效方法。
