chitosan and plga microspheres as drug delivery ... - UniCA Eprints

6. RFP Loaded PLGA Microspheres Prepared by Solvent Evaporation Method6.2.5. Nebulization Studies of PLGA MicrospheresNebulization studies were carried out in order to evaluate the stability and the suitability ofPLGA particles for pulmonary/nasal administration. All these studies were performed byusing both freshly prepared and freeze-dried microspheres. Different analyses were performedon the nebulized samples. As for chitosan microspheres, only the sample trapped in water wasassayed, while the material deposited on the impinger walls was not included.Size of particles was evaluated after the nebulization process and, as can be seen in table 6.3,there was an important decrease of mean particle size and also a significant increase ofpolidispersity index. The decrease on mean size during nebulization can be explained takinginto account that during this process small particles can be nebulized easily. Nebulizationproved that PLGA microspheres, prepared during this work, were multidimensional as it isshown by the high P.I. value. In fact, three different microsphere populations were obtained inthe three different impinger stages. The increase in P.I. could also be related to the fact thatsize analysis was carried out by DLLS, whose sensitivity is not really appropriate for particlesin the micron range.Table 6.3:Particle Size of Spray-Dried Microspheres Before and After NebulizationProcessParticle Size (nmParticle SizeFormulation± SD)P.I ± SD(nm ± SD)P.I ± SDBefore nebulizationAfter nebulizationPLGA 1 2563 ± 49.32 0.192 ± 0.030 1073 ± 35.11 0.778 ± 0.053PLGA 2 2606 ± 61.10 0.203 ± 0.049 1166 ± 32.61 0.857 ± 0.013For all microsphere formulations nebulization efficiency and drug leakage after nebulizationwere evaluated. Both these parameters depend on the stability of particles.As can be seen in figure 6.3 all formulations showed a good nebulization efficiency (NE%)from 72% for PLGA 1 obtained by adding RFP in the organic phase, to 65% for PLGA 2obtained by adding RFP in the aqueous phase. During the nebulization process, part of thedrug can be lost as a consequence of different processes. In fact, some particles, which are toobig, can not be nebulized while others can be disrupted during the process. The little lowerNE% of PLGA 2 formulation is probably connected to the preparation method. In fact, byadding RFP in the aqueous phase it is possible to have some drug on the particle surface, fromwhich can be lose easily during the nebulization process.94