Production of polycaprolactone nanoparticles with low polydispersity index in a tubular recirculating system by using a multifactorial design of experiments

Encapsulation and controlled release of substances using polymeric nanoparticles require that these have a high reproducibility, homogeneity, and control over their properties (diameter and polydispersity), especially when they are to be used in medical, pharmaceutical, or nutritional applications among others. In conventional production systems, it is tough to ensure these characteristics; hence, the cost increases when we try to control these properties. This paper shows a comparison between a recirculating system and the standard nanoprecipitation technique for producing polymeric nanoparticles. In previous investigations, we evaluate the effect of recirculating flow and the ratio between the organic and aqueous phase. For this paper, we evaluated the effect of polymer and surfactant concentrations using a multifactorial design of experiments on the recirculating system and on the standard nanoprecipitation system. The response of the design was the average diameter of the nanoparticles and polydispersity index. Finally, we found that the polymer and surfactant concentrations could change the average diameter and polydispersity index of the nanoparticles obtained. On the other hand, it was found that the effect of the polymer concentration was stronger than the surfactant concentration to reduce the average diameter of the nanoparticles. The results of the present study show that the proposed recirculation system presents a high potential to produce polymer nanoparticles with good morphological characteristics, particle size distributions in the nano range, and with a low polydispersity. The average mean size of nanoparticles of polycaprolactone for the design using the recirculating system was of 61 to 140 nm and the values of polydispersity index PDI for this design were between 0.097 and 0.22, while for the design using the standard nanoprecipitation technique, the obtained diameters were 74 to 176 nm and the polydispersity was between 0.26 and 0.41.