FREEZE-DRYING OF DRUG-FREE AND DRUG-LOADED SOLID LIPID NANOPARTICLES (SLN)

Solid lipid nanoparticles (SLN) of a quality acceptable for i.v. admin istration were freeze-dried. Dynasan 112 and Compritol ATO 888 were us ed as lipid matrices for the SLN, stabilisers were Lipoid S 75 and pol oxamer 188, respectively. To study the protective effect of various ty pes and concentrations of cryoprotectants (e.g. carbohydrates), freeze -thaw cycles were carried out as a pre-test. The sugar trehalose prove d to be most effective in preventing particle growth during freezing a nd thawing and also in the freeze-drying process. Changes in particle size distribution during lyophilisation could be minimised by optimisi ng the parameters of the lyophilisation process, i.e. freezing velocit y and redispersion method. Lyophilised drug-free SLN could be reconsti tuted in a quality considered suitable for i.v. injection with regard to the size distribution. Loading with model drugs (tetracaine, etomid ate) impairs the quality of reconstituted SLN. However, the lyophilisa te quality is sufficient for formulations less critical to limited par ticle growth, e.g. freeze-dried SLN for oral administration. (C) 1997 Elsevier Science B.V.