Investigation of Critical Variables of Core–Shell Polymer Lipid Hybrid Nanoparticles by Using Plackett-Burman Screening Design

The poor entrapment efficiency (%EE) and drug loading in hydrophobic carrier matrix creates hurdles in delivery of water soluble drugs by nanoparticles. To overcome this problem, advanced and tunable core–shell polymer lipid hybrid nanoparticles (CSPLHNs) based robust architecture has been engineered to facilitate the myriad of therapeutic functionalities of hydrophilic molecule within single delivery system which comprise of unique positive attributes of both polymeric nanoparticles and liposomes. The aim of present investigation was to screen and understand the influence of significant formulation and process variables by employing Plackett-Burman screening design in the development of CSPLHNs prepared by W/O/W double emulsification method for the improvement of %EE of water soluble drug. A total of 12 experiments were run for screening of 11 crucial independent variables namely the lipid to polymer ratio, concentration of internal and external surfactant, amount of polymer, organic to aqueous solvent ratio, type of solvent and drug, sonication time and amplitude, stirring speed and temperature by assessing their effect on response variables namely, particle size, %EE and polydispersity index. The statistical analysis of the results allowed determining the most influencing factors. All the regression models yielded a good fit with high correlation coefficient. The pareto chart depicted that among all the independent variables, lipid to polymer ratio, concentration of external surfactant, amount of polymer and organic to aqueous solvent ratio exerted a most significant effect (p < 0.05) on the response variables. Other formulation and process variables did not have a significant impact on CSPLHNs properties and can be used within the limits in future study. By selecting appropriate variables, CSPLHNs of narrow particle size with high %EE can be prepared for water soluble drug. The study can, therefore enable the formulator to select critical variables for development of desired CSPLHNs by decreasing experimentation during formulation.