Stability and freeze-drying of cyclosporine loaded poly(D,L lactide-glycolide) carriers

The present paper describes the stability of poly (D,L-lactide-glycolide) n anoparticles (PLGA NP) and microspheres (MS), either alone or loaded with c yclosporine (CyA), stored at 8 degrees C and room temperature (RT). Freeze- drying of these formulations was evaluated as an alternative method to achi eve long term stability. A significant polymer rupture was detected during PLGA MS preparation by solvent evaporation, which correlated with the stirr ing rates used for the formation of the primary emulsion. On the other hand , the polymer remained unchanged during NP formation. After 6 months of sto rage, PLGA NP of a size below 80 nm aggregated when stored at RT whereas no changes of particle size were observed for the remaining formulations and experimental conditions. Drug entrapment significantly increased by about 9 .5% only during PLGA NP storage at RT. The PLGA molecular weight of NP drop ped at RT being these changes related to the initial particle size and amou nt of CyA incorporated. The same effect was observed at 8 degrees C but onl y the particle size showed a significant influence. The drop of PLGA molecu lar weight observed during storage of MS was not dependent on the storage t emperature but it was directly related to the molecular weights obtained af ter MS preparation. Freeze-drying studies revealed that it was not feasible to maintain the initial PLGA NP characteristics after reconstitution. On t he other hand, MS lyophilized in the absence of cryoprotectants retained th e drug initially entrapped; however, the presence of at least 5% cryoprotec tant was essential to keep the initial particle size. Therefore, PLGA NP an d MS show a significant instability when stored as suspensions. Freeze-dryi ng offers a good alternative to stabilize polymeric MS but the preservation of the PLGA NP characteristics by freeze-drying needs for further investig ations. (C) 1999 Elsevier Science B.V. All rights reserved.