title: Optimization of the lyophilization process for long-term stability of solid-lipid nanoparticles.
abstract: OBJECTIVE
  To optimize a lyophilization protocol for solid-lipid nanoparticles (SLNs) loaded with dexamethasone palmitate (Dex-P) and to compare the long-term stability of lyophilized SLNs and aqueous SLN suspensions at two storage conditions.
  
  
  METHODS
  The effect of various parameters of the lyophilization process on SLN redispersibility was evaluated. A three month stability study was conducted to compare changes in the particle size and drug loading of lyophilized SLNs with SLNs stored as aqueous suspensions at either 4°C or 25°C/60% relative humidity (RH).
  
  
  CONCLUSIONS
  Of nine possible lyoprotectants tested, sucrose was shown to be the most efficient at achieving SLN redispersibility. Higher freezing temperatures, slower freezing rates, and longer secondary drying times were also shown to be beneficial. Loading of the SLNs with Dex-P led to slightly larger particle size and polydispersity index increases, but both parameters remained within an acceptable range. Drug loading and particle shape were maintained following lyophilization, and no large aggregates were detected. During the stability study, significant growth and drug loss were observed for aqueous SLN suspensions stored at 25°C/60% RH. In comparison, lyophilized SLNs stored at 4°C exhibited a consistent particle size and showed <20% drug loss. Other storage conditions led to intermediate results.
  
  
  CONCLUSIONS
  A lyophilization protocol was developed that allowed SLNs to be reconstituted with minimal changes in their physicochemical properties. During a three month period, lyophilized SLNs stored at 4°C exhibited the greatest stability, showing no change in the particle size and a minimal reduction in drug retention.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40506-0046, USA.
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Howard
authors.forename: Xiuling
authors.initials: X
authors.lastname: Lu
authors.forename: Michael
authors.initials: M
authors.lastname: Jay
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dziubla
mesh_terms: D003907:Dexamethasone / Q000737:chemistry; D004355:Drug Stability; D005612:Freeze Drying / Q000379:methods*; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013535:Suspensions / Q000737:chemistry; D013696:Temperature; D014867:Water / Q000737:chemistry
chemical_list: D008055:Lipids; D004364:Pharmaceutical Preparations; D013535:Suspensions; D014867:Water; D003907:Dexamethasone