In situ forming Nimodipine Depot System based on microparticles for the Treatment of Posthaemorrhagic Cerebral Vasospasm
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V | 10 Jan 2013
N Bege, T Renette, T Endres, M Beck-Broichsitter, D Hänggi and T Kissel
The present study was conducted to examine the feasibility of nimodipine loaded PLGA microparticles suspended in Tisseel(™) fibrin sealant as an in situ forming depot system. This device locally placed can be used for the treatment of vasospasm after a subarachnoid hemorrhage. Microparticles were prepared via spray drying by using the vibration mesh spray technology of Nano Spray Dryer B-90. Spherically shaped microparticles with different loadings and high encapsulation efficiencies of 93.3% to 97.8% were obtained. Depending on nimodipine loading (10% - 40%) the particle diameter ranged from 1.9 ± 1.2 μm to 2.4 ± 1.3μm. Thermal analyses using DSC revealed that Nimodipine is dissolved in the PLGA matrix. Also fluorescent dye loaded microparticles were encapsulated in Tisseel(™) to examine the homogeneity of particles. 3D-pictures of the in situ forming devices displayed uniform particle homogeneity in the sealant matrix. Drug release was examined by fluorescence spectrophotometry which demonstrated a drug release proportional to the square root of time. A prolonged drug release of 19.5 h was demonstrated under in vitro conditions. Overall, the Nimodipine in situ forming device could be a promising candidate for the local treatment of vasospasm after a subarachnoid hemorrhage.
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