STABILITY OF CYCLOSPORINE-LOADED POLY-SIGMA-CAPROLACTONE NANOPARTICLES

The aim was to evaluate the long-term stability of cyclosporin A-loade d nanoparticle suspensions, stored at 8 and 25 degrees C. The stabilit y of freeze-dried samples was also investigated. Nanoparticles (NP) of poly-Sigma-caprolactone (P Sigma CL), a biodegradable polymer, were o btained by a modified nanoprecipitation method. A central composite ex perimental design was used to investigate the simultaneous effect of t echnological factors (temperature of the aqueous phase and needle gaug e) and formulation variables (volume of acetone and the amount of poly mer and surfactant). The effect of these variables on the stability of the 100-220 nm particles obtained was evaluated. The percentage of cy closporin A (CyA) encapsulated in the NP suspensions stored at 8 and 2 5 degrees C for at least 3 months remained unaltered. Moreover, there was no change in the size of NP. After 4 months storage, the physical stability of the preparation was affected. NP aggregates could be obse rved by light microscopy. Reconstituted freeze-dried preparations show ed a mean increase of 1% in the incorporated drug and also a considera ble increase in mean size and size distribution. Additional experiment s investigated the effect of freezing temperature (-70 and -196 degree s C) and of 5, 10 and 20% (w/v) cryoprotector (mannitol, sorbitol, glu cose and threalose) on 100 nm particles. The addition of glucose and t hrealose at concentrations >10% permitted adequate reconstitution of t he freeze-dried product with conservation of the encapsulated CyA.