Preparation and Evaluation of Rebamipide Colloidal Nanoparticles Obtained by Cogrinding in Ternary Ground Mixtures
Preparation and Evaluation of Rebamipide Colloidal Nanoparticles Obtained by Cogrinding in Ternary Ground Mixtures
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DOI：
10.3390/colloids4040043
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发表时间：
2020-12-01
影响因子：
2.4
通讯作者：
Hanawa, Takehisa
中科院分区：
文献类型：
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作者：
Kawano, Yayoi;Utsunomiya, Yuiko;Hanawa, Takehisa
摘要口疮性口炎是癌症化疗及放射线治疗的副作用之一。瑞巴派特（RB）口腔炎漱口水作为自由基清除剂。然而，RB难溶于水，导致分散体聚集和沉淀。药物的粒径需要小于100 nm，以使颗粒到达口腔中的粘液层。本研究采用混合式球磨机分别与聚乙烯吡咯烷酮（PVP）、羟丙基纤维素（HPC）和十二烷基硫酸钠（SDS）共磨制备RB纳米粒，并对RB纳米粒的理化性质、水分散稳定性和体外粘液层渗透性进行了评价。通过共研磨，颗粒尺寸减小到约110 nm，并且颗粒的粉末X射线衍射（PXRD）显示出完全宽的晕圈图案，这表明结晶区域减小。此外，与RB晶体相比，RB纳米颗粒的溶解度增加了约4倍，并且改善了粘液层的吸水性和渗透性。结果表明，在RB、PVP或HPC和SDS的三元研磨混合物中，所获得的RB纳米颗粒可以用作口腔炎的制剂。
Aphthous stomatitis is one of the side effects of chemotherapy and radiotherapy in cancer treatment. Rebamipide (RB) mouthwash for stomatitis acts as a radical scavenger. However, RB is poorly soluble in water, which leads to aggregation and precipitation of the dispersoid. The particle size of the drug needs to be less than 100 nm for the particles to reach the mucus layer in the oral cavity. In this study, we attempted to prepare nanoparticles of RB by cogrinding with polyvinylpyrrolidone (PVP) or hydroxypropyl cellulose (HPC) and sodium dodecyl sulfate (SDS) using a mixer ball mill, and evaluated the physicochemical properties of RB nanoparticles, the stability of dispersion in water, and permeation of the mucus layer in vitro. By cogrinding, the particle size decreased to around 110 nm, and powder X-ray diffraction (PXRD) of the particles showed totally broad halo patterns, which suggested a decreased crystalline region. Furthermore, the solubility of RB nanoparticles increased by approximately fourfold compared with RB crystals, and the water dispersibility and permeation of the mucus layer were improved. The results suggest that in a ternary ground mixture of RB, PVP or HPC, and SDS, the RB nanoparticles obtained can be applied as a formulation for stomatitis.