OPTIMIZED PREPARATION OF POLY D,L (LACTIC-GLYCOLIC) MICROSPHERES AND NANOPARTICLES FOR ORAL-ADMINISTRATION

A rotatable central composite design (RCCD) was applied to optimize th e preparation of cyclosporine-loaded poly D,L (lactide-glycolide) (PLA GA) nanoparticles (NP) and microspheres (MS) by solvent displacement a nd solvent evaporation techniques, respectively. The joint influence o f needle gauge, polymer amount and the injection rates on the mean par ticle size, relative standard deviation (RSD), yield and drug encapsul ation percentage in NP were evaluated. With regards to MS, the polymer amount and the stirring rate were evaluated. Scan electron microscopy of MS and NP showed spherical particles with a dense polymeric networ k in the first case. From the statistical analysis of data polynomial equations were generated. The mean particle size ranged from 50 to 150 nm for NP and from 1.5 to 30 mu m for MS. Smallest nanoparticles (46 nm) were obtained by using the lowest polymer amounts, the highest inj ection rates and the lowest needle gauges (r(2) = 0.9443). Under these conditions the drug entrapment percentage was maximum (85.2%), sugges ting the drug might be entrapped and adsorbed on the nanoparticle surf ace. The relative standard deviation was only affected by the polymer amount (r(2) = 0.8034) and the yield rose with the amount of PLAGA (r( 2) = 0.9016). A very important increase in particle size (r(2) = 0.985 5), relative standard deviation (r(2) = 0.9353) and encapsulation perc entage (r(2) = 0.9669) were observed for MS by decreasing emulsificati on stirring rates and increasing polymer amounts, the stirring rate be ing the most significant independent variable (alpha < 0.0001) in all cases. The highest experimental encapsulation value (97.69 +/- 0.78%) correspond to samples prepared from 150 mg of polymer and a global sti rring rate of 2000 rpm. By using response surface diagrams and the mat hematical models proposed, it is possible to easily deduce experimenta l conditions to prepare NP and MS with the desired properties.