Preparation and stabilization of nifedipine lipid nanoparticles

Design methods of nanoparticle formulations are divided into a break-down method and a build-up method. Furthermore, the former is further divided into dry and wet processes. For drug nanoparticle preparations, the wet process is generally employed, and organic solvents are used in most formulations. In this study, we investigated the preparation of nifedipine (NI) nanoparticles without using any organic solvent. NI nanoparticles with a mean particle size of approximately 50 nm could be prepared without organic solvent by a combination of roll mixing and high-pressure homogenization. The X-ray diffraction peak of the sample prepared by roll mixing was present at an identical position (2θ) to that of NI crystals, showing that no peak shift was induced by interaction with lipid. These findings clarified that most NI remained as crystals in lipid.To maintain the particle size of the nanoparticles in suspension for a long time, a method of adding gelatin powder to the NI-lipid nanoparticle suspension, dissolving the mixture by heating, and then solidifying by cooling was investigated. The mean particle size of the sample was about 55 nm, and that after heat-liquefaction of the NI-lipid nanoparticle suspension gelated at 5 °C for 24 h was also about 55 nm, showing that the nanoparticle condition was retained.