In situ forming nimodipine depot system based on microparticles for the treatment of posthemorrhagic cerebral vasospasm

Eur J Pharm Biopharm. 2013 May;84(1):99-105. doi: 10.1016/j.ejpb.2012.12.016. Epub 2013 Jan 5.

Abstract

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 93.3-97.8% were obtained. Depending on nimodipine loading (10-40%), the particle diameter ranged from 1.9 ± 1.2 μm to 2.4 ± 1.3 μm. 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 19.5h 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.

MeSH terms

  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacokinetics
  • Microspheres*
  • Nimodipine / chemistry*
  • Nimodipine / pharmacokinetics
  • Subarachnoid Hemorrhage*
  • Treatment Outcome
  • Vasospasm, Intracranial*

Substances

  • Delayed-Action Preparations
  • Nimodipine