Screening of critical variables in fabricating polycaprolactone nanoparticles using Neuro Fuzzy Logic.

Journal: International journal of pharmaceutics
Published Date:

Abstract

In this work, we used the artificial intelligence tool known as neurofuzzy logic (NFL) for fabricating uniform nanoparticles of polycaprolactone by the nanoprecipitation method with a focus on stabilizer selection. The adaptability of NFL assisted the decision-making on different manufacturing and formulation conditions. The nanoprecipitation method can be summarized as mixing a poorly water-soluble polymer solution with water and its consequent precipitation. Although nanoprecipitation seems simple, the process is highly variable to even slight modifications, leading to polydispersity and nanoparticle aggregation. Here, the NFL model established relationships between mixing conditions, different stabilizers and solvents, among other parameters. Seven parameters measured by dynamic light scattering and laser doppler electrophoresis were modelized with high predictability using NFL tool, as a function of the raw materials and operation conditions. The model allowed the principal component analysis to be carried out, showing that the selection of a stabilizer is the most critical parameter for avoiding nanoparticle aggregation. Then, inputs related to fluid dynamics were relevant to tune the characteristics of the stabilized nanoparticles even further. NFL model showed great potential to support pharmaceutical research by finding subtle relationships between several variables, even from incomplete or fragmented data, which is common in pharmaceutical development.

Authors

  • Miguel O Jara
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santos Dumont 964, 4to piso, Of. 09, Independencia, 8380494 Santiago, Chile; Molecular Pharmaceutics and Drug Delivery Division, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, 78712 Austin, TX, USA(1).
  • Mariana Landin
    Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain.
  • Javier O Morales
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santos Dumont 964, 4to piso, Of. 09, Independencia, 8380494 Santiago, Chile; Advanced Center for Chronic Diseases (ACCDiS), 8380494 Santiago, Chile; Center of New Drugs for Hypertension (CENDHY), 8380494 Santiago, Chile. Electronic address: jomorales@ciq.uchile.cl.