Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, BMC, P.O. Box 580, SE-751 23, Uppsala, Sweden.
Division of Nanotechnology and Functional Materials, Department of Engineering Sciences, Uppsala University, SE-751 21, Uppsala, Sweden.
AAPS PharmSciTech. 2018 Oct;19(7):2859-2865. doi: 10.1208/s12249-018-1024-1. Epub 2018 Jun 6.
Effective and compound-sparing methods to evaluate promising drug delivery systems are a prerequisite for successful selection of formulations in early development stages. The aim of the study was to develop a small-scale in situ method to determine drug release and supersaturation in highly concentrated suspensions of enabling formulations. Mesoporous magnesium carbonate (MMC), which delivers the drug in an amorphous form, was selected as a drug carrier. Five model compounds were loaded into the MMC at a 1:10 ratio using a solvent evaporation technique. The μDiss Profiler was used to study the drug release from MMC in fasted-state simulated intestinal fluid. To avoid extensive light scattering previously seen in particle-rich suspensions in the μDiss Profiler, an in-house-designed protective nylon filter was placed on the in situ UV probes. Three types of release experiments were conducted for each compound: micronized crystalline drug with MMC present, drug-loaded MMC, and drug-loaded MMC with 0.01% w/w hydroxypropyl methyl cellulose. The nylon filters effectively diminished interference with the UV absorption; however, the release profiles obtained were heavily compound dependent. For one of the compounds, changes in the UV spectra were detected during the release from the MMC, and these were consistent with degradation of the compound. To conclude, the addition of protective nylon filters to the probes of the μDiss Profiler is a useful contribution to the method, making evaluations of particle-rich suspensions feasible. The method is a valuable addition to the current ones, allowing for fast and effective evaluation of advanced drug delivery systems.
有效且节约成本的方法来评估有前途的药物输送系统是成功选择早期开发阶段制剂的前提。本研究的目的是开发一种小规模的原位方法，以确定高浓度悬浮液中赋形剂的药物释放和过饱和度。选择介孔碳酸镁（MMC）作为药物载体，以无定形形式输送药物。采用溶剂蒸发技术，将五种模型化合物以 1:10 的比例装入 MMC。使用 μDiss Profiler 研究 MMC 在空腹模拟肠液中的药物释放。为了避免 μDiss Profiler 中先前在富含颗粒的悬浮液中看到的广泛光散射，在原位 UV 探头放置了一个内部设计的保护尼龙过滤器。对每种化合物进行了三种类型的释放实验：有 MMC 的微米化结晶药物、载药 MMC 和载药 MMC 加 0.01%w/w 羟丙基甲基纤维素。尼龙过滤器有效地减少了对 UV 吸收的干扰；然而，得到的释放曲线严重依赖于化合物。对于其中一种化合物，在从 MMC 释放过程中检测到 UV 光谱的变化，这些变化与化合物的降解一致。总之，向 μDiss Profiler 的探头添加保护尼龙过滤器是对该方法的有益贡献，使评估富含颗粒的悬浮液成为可能。该方法是当前方法的有益补充，允许快速有效地评估先进的药物输送系统。
