title: Stability of cyclosporine-loaded poly-sigma-caprolactone nanoparticles.
abstract: The aim was to evaluate the long-term stability of cyclosporin A-loaded nanoparticle suspensions, stored at 8 and 25 degrees C. The stability of freeze-dried samples was also investigated. Nanoparticles (NP) of poly-sigma-caprolactone (P sigma CL), a biodegradable polymer, were obtained by a modified nanoprecipitation method. A central composite experimental design was used to investigate the simultaneous effect of technological factors (temperature of the aqueous phase and needle gauge) and formulation variables (volume of acetone and the amount of polymer and surfactant). The effect of these variables on the stability of the 100-220 nm particles obtained was evaluated. The percentage of cyclosporin A (CyA) encapsulated in the NP suspensions stored at 8 and 25 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 observed by light microscopy. Reconstituted freeze-dried preparations showed a mean increase of 1% in the incorporated drug and also a considerable increase in mean size and size distribution. Additional experiments investigated the effect of freezing temperature (-70 and -196 degrees C) and of 5, 10 and 20% (w/v) cryoprotector (mannitol, sorbitol, glucose and threalose) on 100 nm particles. The addition of glucose and threalose at concentrations > 10% permitted adequate reconstitution of the freeze-dried product with conservation of the encapsulated CyA.
authors.affiliation: Dpto Farmacia y Tecnología Farmacéutica, Universidad de Alcalá, Alcalá de Henares (Madrid), Spain.
authors.forename: J
authors.initials: J
authors.lastname: Molpeceres
authors.forename: M R
authors.initials: MR
authors.lastname: Aberturas
authors.forename: M
authors.initials: M
authors.lastname: Chacón
authors.forename: L
authors.initials: L
authors.lastname: Berges
authors.forename: M
authors.initials: M
authors.lastname: Guzmán
mesh_terms: D003080:Cold Temperature; D016572:Cyclosporine / Q000737:chemistry* / Q000378:metabolism; D004339:Drug Compounding / Q000379:methods / Q000706:statistics & numerical data; D004355:Drug Stability; D004356:Drug Storage; D005612:Freeze Drying; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry* / Q000378:metabolism; D013535:Suspensions; D013696:Temperature
chemical_list: D011091:Polyesters; D013535:Suspensions; C016240:polycaprolactone; D016572:Cyclosporine