层状双氢氧化物(LDHs)是高效的药物递送系统,由于它们嵌入或吸附生物材料的能力,柔性结构,溶胀性能,高稳定性,良好的生物相容性,易于合成。苯妥英(PHT)是一种抗癫痫BCS(生物制药分类系统)II类药物,呈现低水溶性。因此,目前的研究旨在增加其溶解度,溶出度,和生物利用度。PHT嵌入到原位形成的MgAl-LDH中,FTIR证实成功嵌入形成MgAl-PHT-LDH。PXRD,DSC,和TGA。粒度和形态的检查(通过光子相关光谱和电子显微镜,分别)证实了纳米结构LDH的形成和插层。嵌入使PHT在25°C下在0.1NHCl和磷酸盐缓冲液(pH6.8)中的饱和溶解度分别提高了6.57和10.5倍。用于MgAl-PHT-LDH片剂配方的所选药物赋形剂粉末混合物在两个预压缩参数(静止角,堆积密度,振实密度,卡尔的索引,和豪斯纳比率)和片剂特征(重量变化,厚度,硬度,脆性,含量均匀性,和崩解时间)。与未加工的PHT片剂相比,MgAl-PHT-LDH片剂在所有时间点显示更好的PHT溶出。基于通过UPLC-ESI-MS/MS血清分析两种形式的PHT的血清水平,在两组SpragueDawley大鼠中测试了MgAl-PHT-LDH片剂和未加工的PHT片剂的口服生物利用度。与未加工的PHT片剂相比,MgAl-PHT-LDH片剂的相对生物利用度为130.15%,证实了MgAl-PHT-LDH的显著更高的口服生物利用度。总之,MgAl-PHT-LDH可以提供一种增强溶解度的策略,溶出度,因此PHT的生物利用度,能够评估MgAl-PHT-LDH片在较低PHT剂量下治疗癫痫发作的临床疗效。
Layered double hydroxides (LDHs) are highly effective drug delivery systems, owing to their capacity to intercalate or adsorb biomaterials, flexible structure, swelling property, high stability, good biocompatibility, and ease of synthesis. Phenytoin (PHT) is an antiseizure BCS (Biopharmaceutics Classification System) class II drug, presenting low aqueous solubility. Therefore, the current study aimed at increasing its solubility,
dissolution, and bioavailability. PHT was intercalated to the MgAl-LDH formed in situ and successful intercalation to form MgAl-PHT-LDH was confirmed by FTIR, PXRD, DSC, and TGA. Examination of particle size and morphology (by photon correlation spectroscopy and electron microscopy, respectively) confirmed the formation and intercalation of nanostructured LDH. Intercalation enhanced the saturation solubility of PHT at 25°C in 0.1N HCl and phosphate buffer (pH 6.8) by 6.57 and 10.5 times respectively. The selected drug excipient powder blend for the formulation of MgAl-PHT-LDH tablets exhibited satisfactory properties in both pre-compression parameters (angle of repose, bulk density, tapped density, Carr\'s index, and Hausner ratio) and tablet characteristics (weight variation, thickness, hardness, friability, content uniformity, and disintegration time). MgAl-PHT-LDH tablets showed better
dissolution of PHT compared to unprocessed PHT tablets at all time points. Oral bioavailability of MgAl-PHT-LDH tablets and unprocessed PHT tablets was tested in two groups of Sprague Dawley rats based on analysis of serum levels of both forms of PHT by UPLC-ESI-MS/MS serum. MgAl-PHT-LDH tablets demonstrated a relative bioavailability of 130.15% compared to unprocessed PHT tablets, confirming a significantly higher oral bioavailability of MgAl-PHT-LDH. In conclusion, MgAl-PHT-LDH could provide a strategy for enhancing solubility,
dissolution, and thereby bioavailability of PHT, enabling the evaluation of theclinical efficacy of MgAl-PHT-LDH tablets for the treatment of seizures at lower PHT doses.