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Jun 6, 2018

A Modified In Situ Method to Determine Release from a Complex Drug Carrier in Particle-Rich Suspensions


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.

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