Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, West Bengal 700054, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Kolkata, West Bengal 700054, India.
Nanoscale. 2024 Oct 31;16(42):19786-19805. doi: 10.1039/d4nr03137g.
This study investigated the formulation and characterization of rebamipide nanocrystals (REB-NCs) to enhance the solubility and permeability of rebamipide, an anti-ulcer medication known for its low aqueous solubility and permeability, classified as BCS class IV. Employing high-pressure homogenization and wet milling techniques, we successfully achieved nanonization of rebamipide, resulting in stable nanosuspensions that were subsequently freeze-dried to produce REB-NCs with an average particle size of 223 nm. Comprehensive characterization techniques, including Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC) confirmed the crystalline nature of the nanocrystals and their compatibility with the selected excipients. The saturation solubility study revealed a remarkable three-fold enhancement in PBS pH 7.4 compared to rebamipide API, indicating the effectiveness of the nanocrystal formulation in improving drug solubility. Furthermore, 3D permeability assessments conducted on Caco-2 cell monolayers demonstrated an noticeable increase in the permeability of REB-NCs relative to the pure active pharmaceutical ingredient (API), highlighting the promise of this formulation to enhance drug absorption. The dissolution profile of the nanocrystal tablets exhibited immediate release characteristics, significantly outperforming conventional formulations in terms of the dissolution rate. This research underscores the potential of nanomilling as a scalable, environment-friendly, and less toxic approach to significantly enhance the bioavailability of rebamipide. By addressing the challenges associated with the solubility and permeability of poorly water-soluble drugs, our outcome offers insightful information into developing efficient nanomedicine strategies for enhancing therapeutic outcomes.
本研究旨在制备和表征瑞巴派特纳米晶体（REB-NCs），以提高瑞巴派特（一种抗溃疡药物）的溶解度和渗透性。瑞巴派特的水溶性和渗透性较差，被归类为 BCS 分类 IV 类药物。本研究采用高压均质和湿磨技术成功实现了瑞巴派特的纳米化，得到了稳定的纳米混悬液，随后将其冷冻干燥，制备出平均粒径为 223nm 的 REB-NCs。傅里叶变换红外光谱（FTIR）、扫描电子显微镜（SEM）、X 射线衍射（XRD）和差示扫描量热法（DSC）等综合表征技术证实了纳米晶体的结晶性质及其与所选赋形剂的相容性。溶解度研究表明，在 PBS pH7.4 中，REB-NCs 的饱和溶解度比原料药提高了约三倍，表明纳米晶体配方在提高药物溶解度方面的有效性。此外，在 Caco-2 细胞单层上进行的 3D 渗透性评估表明，REB-NCs 的渗透性相对于纯原料药显著提高，这表明该配方有潜力增强药物吸收。纳米晶体片的溶出曲线表现出即刻释放的特点，在溶出速率方面明显优于常规制剂。这项研究强调了纳米研磨作为一种可扩展、环保且毒性较小的方法，具有显著提高瑞巴派特生物利用度的潜力。通过解决水溶性差的药物的溶解度和渗透性问题，我们的研究结果为开发提高治疗效果的高效纳米医学策略提供了有价值的信息。
