Drug release and release mechanism of prednisolone loaded solid lipid nanoparticles

Solid lipid nanoparticles (SLN) are a colloidal carrier system for the controlled delivery of drugs. To study the potential of SLN to achieve prolonged drug release prednisolone was chosen as a lipophilic model drug. The cold and the hot homogenisation method were used to produce prednisolone loaded SLN. To investigate the drug release from SLN the USP XXII paddle method was employed. Atomic force microscopy (AFM) was applied for the characterisation of the shape and the surface of SLN. By applying the cold homogenisation technique SLN dispersions were obtained which show in vitro only a minor burst and a prolonged drug release over a monitored period up to 5 weeks. In contrast, the release profile of SLN produced by the hot homogenisation technique is characterised by a pronounced fast initial drug release (burst effect) in the first five minutes which is followed by a prolonged drug release. The biphasic release profile is generated by the heterogeneous particle structure and by partitioning processing during and after the production. The partitioning mechanism is strongly affected by the solubility of the drug in the water phase. Thus by applying low production temperatures and surfactant concentrations the burst effect can be minimised. In conclusion, choosing appropriate production temperatures and surfactant concentrations a desired in vitro release profile can be obtained. These result show that SLN are suitable as carriers for prolonged drug release.