Section for Pharmaceutical Design and Drug Delivery, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Int J Pharm. 2013 May 20;448(2):373-81. doi: 10.1016/j.ijpharm.2013.03.031. Epub 2013 Mar 25.
In recent years, there has been a particular interest in bioadhesive formulations for oromucosal drug delivery as this may promote prolonged local therapy and enhanced systemic effect. Saliva plays a vital role in oromucosal drug absorption by dissolving the drug and presenting it to the mucosal surface. However, the rheological, chemical, and interfacial properties of this complex biological fluid may strongly affect the adhesion of bioadhesive formulations. There is a need for well characterized in vitro models to assess the bioadhesive properties of oral dosage forms for administration in the oral cavity. Thus we aimed at developing an advanced ex vivo buccal retention model, with focus on choosing a physiologically relevant irrigation media closely resembling human saliva. Spray dried chitosan microparticles containing metformin hydrochloride as an example of a small hydrophilic drug, were employed as bioadhesive formulations. Chewing-stimulated human whole saliva was collected and characterized for use in retention studies in comparison with four artificial irrigation media; phosphate buffer, Saliva Orthana(®), porcine gastric mucin base media (PGM3), and xanthan gum based media (XG2). Retention of metformin, applied as spray dried microparticles on porcine buccal mucosa, greatly depended on the characteristics of the irrigation media. When rheology of the irrigation media was examined, changes in retention profiles could be interpreted, as irrigation media containing mucin and xanthan gum possessed a higher viscosity than phosphate buffer, which led to longer retention of the drug due to better hydration of the mucosa and the spray dried microparticles. Metformin retention profiles were comparable when human saliva, Saliva Orthana(®), or PGM3 were used as irrigation media. Moreover, PGM3 displayed physico-chemical properties closest to those of human saliva with regard to pH, protein content and surface tension. Saliva Orthana(®) and PGM3 are therefore considered as suitable irrigation media for further retention studies.
近年来，人们对口腔粘膜给药剂型的生物粘附制剂特别感兴趣，因为这可能促进局部治疗时间延长和全身效应增强。唾液在口腔粘膜药物吸收中起着至关重要的作用，它溶解药物并将其呈递到粘膜表面。然而，这种复杂生物流体的流变学、化学和界面特性可能会强烈影响生物粘附制剂的粘附性。需要有经过良好表征的体外模型来评估口腔给药剂型的生物粘附特性，以便在口腔内给药。因此，我们旨在开发一种先进的离体颊部保留模型，重点是选择一种生理相关的灌洗介质，使其更接近人类唾液。以含有盐酸二甲双胍的喷雾干燥壳聚糖微球为例，作为一种小亲水性药物的生物粘附制剂。收集并表征咀嚼刺激的人全唾液，用于与四种人工灌洗介质（磷酸盐缓冲液、Saliva Orthana ® 、猪胃粘蛋白基础介质（PGM3）和黄原胶基介质（XG2））进行保留研究。喷干壳聚糖微球在猪颊粘膜上的盐酸二甲双胍的保留率极大地取决于灌洗介质的特性。当检查灌洗介质的流变学特性时，可以解释保留曲线的变化，因为含有粘蛋白和黄原胶的灌洗介质的粘度高于磷酸盐缓冲液，这导致药物保留时间延长，这是由于粘膜和喷干微球更好的水合作用。当使用人唾液、Saliva Orthana ® 或 PGM3 作为灌洗介质时，盐酸二甲双胍的保留曲线相似。此外，PGM3 在 pH 值、蛋白质含量和表面张力方面与人类唾液的理化性质最接近。因此，Saliva Orthana ® 和 PGM3 被认为是适合进一步保留研究的灌洗介质。
