Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
J Pharm Biomed Anal. 2012 Dec;71:27-34. doi: 10.1016/j.jpba.2012.07.024. Epub 2012 Jul 31.
Upon subcutaneous administration, the distribution of drug between the delivery vehicle and the biological tissue critically affects the absorption of drug substances. Utilization of physical models resembling the native tissues appears promising for obtaining a detailed understanding of the performance of drug delivery systems based on in vitro experiments. The objective of this study was to evaluate a UV imaging-based method for real-time characterization of the release and transport of piroxicam in hydrogel-based subcutaneous tissue mimics/surrogates. Piroxicam partitioning from medium chain triglyceride (MCT) into 0.5% (w/v) agarose or 25% (w/v) F127-based hydrogels was investigated by monitoring the concentration profiles of the drug in the gels. The effect of pH on piroxicam distribution and diffusion coefficients was studied. For both hydrogel systems, the diffusion of piroxicam in the gels was not affected significantly by the pH change from 4.0 to 7.4 but a considerable change in the oil-gel distribution coefficients was found (24 and 34 times less at pH 7.4 as compared those observed at pH 4.0 for F127 and agarose gels, respectively). In addition, the release and transport processes of piroxicam upon the injection of aqueous or MCT solutions into an agarose-based hydrogel were investigated by UV imaging. The spatial distribution of piroxicam around the injection site in the gel matrix was monitored in real-time. The disappearance profiles of piroxicam from the injected aqueous solution were obtained. This study shows that the UV imaging methodology has considerable potential for characterizing transport properties in hydrogels, including monitoring the real-time spatial concentration distribution in vitro after administration by injection.
皮下给药时，药物在传递载体和生物组织之间的分布会极大地影响药物物质的吸收。利用类似于天然组织的物理模型似乎有望深入了解基于体外实验的药物传递系统的性能。本研究的目的是评估一种基于 UV 成像的方法，用于实时描述吡罗昔康在水凝胶型皮下组织模拟物/替代物中的释放和传输。通过监测凝胶中药物的浓度分布，研究了吡罗昔康从中链甘油三酯（MCT）向 0.5%（w/v）琼脂糖或 25%（w/v）F127 水凝胶中的分配。研究了 pH 对吡罗昔康分布和扩散系数的影响。对于这两种水凝胶系统，pH 从 4.0 变为 7.4 不会显著影响吡罗昔康在凝胶中的扩散，但发现油-凝胶分配系数发生了相当大的变化（与 pH 4.0 相比，F127 和琼脂糖凝胶的分配系数分别减少了 24 倍和 34 倍）。此外，通过 UV 成像研究了将水性或 MCT 溶液注入琼脂糖水凝胶中时吡罗昔康的释放和传输过程。实时监测了吡罗昔康在凝胶基质中注射部位周围的空间分布。获得了从注射的水性溶液中消失的吡罗昔康的曲线。本研究表明，UV 成像方法在水凝胶中的传输特性具有很大的潜力，包括在注射后通过体外实时监测分布。
