Department of Pharmaceutical Nanotechnology, Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, Iran.
Cellular and Molecular Biology Research Center, Larestan University of Medical Sciences, Larestan, Iran.
Drug Dev Ind Pharm. 2022 Aug;48(8):343-354. doi: 10.1080/03639045.2022.2113405. Epub 2022 Sep 6.
Poorly water-soluble drugs like sorafenib tosylate (SFB) can be made more soluble and orally bioavailable using a biocompatible hydrophilic matrix yields amorphous or microcrystalline drugs with high stability and low recrystallization risk. Mesoporous starch (MPS) due to its edibility, biodegradability, high surface area, and confined pores. In this study, MPS, either alone or in combination with polyvinylpyrrolidone (PVP), was employed for improving SFB oral bioavailability. To this aim, MPS was prepared in three steps: gelatinization, solvent exchange, and vacuum drying, after which it was used to incorporate SFB at various ratios using the immersion/solvent evaporation technique. Nitrogen adsorption/desorption analysis, Fourier transform infrared spectrometry (FTIR), field emission scanning electron microscopy (FE-SEM), powder X-ray diffraction (XRD) crystallography, and differential scanning calorimetry (DSC) were used to characterize SFB-loaded and drug-free samples, which confirmed the successful preparation of mesoporous structures with desirable uniform porosity, small pore size (about 5.3 nm), and specific surface area of about 24 m/g. dissolution testing revealed that the SFB dissolution rate increased substantially for the loaded MPS or MPS-PVP samples. Furthermore, when SFB was loaded in MPS-PVP, single-dose pharmacokinetics in rats confirmed an enhanced oral absorption kinetic. Therefore, impregnation of poorly soluble drugs such as SFB in the PVP-modified MPS excipient, which is constructed from a combination of mesoporous materials and a drug recrystallization inhibitor such as hydrophilic polymers, is proposed as a promising strategy for desirable enhancements in drug solubility, oral bioavailability, and efficacy.
对于水溶性差的药物，如索拉非尼甲苯磺酸盐（SFB），可以使用生物相容性的亲水性基质来增加其溶解度和口服生物利用度，从而得到具有高稳定性和低重结晶风险的无定形或微晶药物。由于其可食用性、生物降解性、高比表面积和受限孔，中孔淀粉（MPS）。在这项研究中，MPS 单独或与聚乙烯吡咯烷酮（PVP）联合使用，以提高 SFB 的口服生物利用度。为此，MPS 通过三步制备：糊化、溶剂交换和真空干燥，然后使用浸渍/溶剂蒸发技术将 SFB 以不同比例掺入其中。氮气吸附/解吸分析、傅里叶变换红外光谱（FTIR）、场发射扫描电子显微镜（FE-SEM）、粉末 X 射线衍射（XRD）结晶学和差示扫描量热法（DSC）用于表征负载 SFB 和无药物的样品，证实了具有理想均匀孔隙率、小孔径（约 5.3nm）和比表面积约 24m/g 的中孔结构的成功制备。溶解试验表明，负载 MPS 或 MPS-PVP 样品的 SFB 溶解速率大大提高。此外，当 SFB 负载在 MPS-PVP 中时，大鼠的单剂量药代动力学证实了口服吸收动力学的增强。因此，将水溶性差的药物（如 SFB）浸渍在由中孔材料和亲水聚合物等药物重结晶抑制剂组成的 PVP 改性 MPS 赋形剂中，被提议作为提高药物溶解度、口服生物利用度和疗效的一种有前途的策略。
