Production & stability of stavudine solid lipid nanoparticles-From lab to industrial scale

The production of stavudine-loaded solid lipid nanoparticles (SLN) for intravenous injection was scaled up from lab scale (40g) to medium scale (10 kg) and large scale (20/60 kg). The SLN were produced by high pressure homogenization of stavudine lipid melt dispersed in hot surfactant solution (pre-emulsion) applying 800 bar pressure. Employed were piston-gap homogenizers with increasing capacity (APV Gaulin products LAB 40, LAB 60 and Gaulin 5.5; and Avestin C50), using them in the continuous (circulation) and discontinuous mode. Size analysis was performed by photon correlation spectroscopy (PCS), laser diffractometry and light microscopy. At lab scale a PCS size of 53 nm was obtained. At the same pressure, all homogenizers on larger scale yielded a size in the range of the lab scale product (35-70 nm). Differences were found in the size as a function of circulation time (size increase or size reduction with time) and the number of cycles required (1 or 5) for the optimal product. The stavudine SLN formulation (2% lipid content, high surfactant to lipid ratio) showed a different behavior to conventional higher concentrated SLN suspensions or nanoemulsions (10% or 20% lipid/oil, low surfactant to lipid ratio). In general, smallest sizes were obtained in the discontinuous mode after just one homogenization cycle. The continuous production mode was only efficient with a 10 kg batch size using the LAB 60. In addition, the long-term stability over 1 year was monitored at refrigeration, room temperature and at 40 degrees C to assess a potential effect of the homogenizer type on stability. All batches at room temperature and below were stable, only a negligible increase in size was observed. (C) 2010 Elsevier B.V. All rights reserved.