QbD-based Formulation Development and Characterization of Isradipine Loaded Freeze-Dried Nanoparticles

Abstract

Objective: The basis of this research was to implement a quality by design technique to develop and optimize Isradipine-loaded PLGA-based nanoparticles (NPs).

Significance: The current study employed a nanoprecipitation method to make PLGA-based nanoparticles using Poloxamer 407 as a stabilizer, then applied a QbD strategy to optimize them.

Method: This technique proved efficient for investigating the multiple components and their interactions that influence the product by using the Design of Experiment (DoE). The initial variables screening using a Taguchi orthogonal array design, followed by a Central Composite Design (CCD) to attain the critical quality attributes (CQAs) such as; % drug release, particle size(nm), Zeta potential(mV) and PDI values.

Results: The optimized PLGA nanoparticles exhibited 95.43%, 169.59nm, -37.36 mV and 0.368, respectively. The solid-state characterization was carried out by FT-IR, DSC, SEM and P-XRD analysis. However, there was no interaction between the drug and the excipients, as revealed from FT-IR and DSC studies. The SEM results of the optimized formulation exhibited spherical and smooth nature. P-XRD results indicated the crystalline nature of the pure drug, which was minimized concerning the optimized nanoparticles depicting its amorphous form. Conclusions: Furthermore, the optimized PLGA-based freeze-dried nanoparticles have improved release kinetics compared to the pure drug.