QbD decorated ellagic acid loaded polymeric nanoparticles: Factors influencing desolvation method and preliminary evaluations

Abstract

Polymeric nanoparticles are one of the emerging drug delivery systems in the field of oncology. Ellagic acid is a polyphenolic compound with vast effects like anti-cancer, anti-viral, and anti-oxidant. The ellagic acid nanoparticles was prepared by desolvation method. Formulating ellagic acid NPs using BSA enhances the stability and solubility of ellagic acid. Quality by design (QbD) based approach was adopted to improve the final quality and effectiveness of the formulation. The Critical quality attribute (CQAs) was defined and risk assessment was performed with the help of the Ishikawa fishbone diagram. Solubility analysis was done for the drug with methanol, ethanol, water, and acetone. Preliminary studies were performed to study the effect of type of desolvating agent, the concentration of polymer the pH of the polymer solution, amount of desolvating agent on the particle size and entrapment efficiency of the nanoparticles. A greater quantity of desolvating agent results in a narrower particle size because of thorough desolvation, and the increased encapsulation efficiency is linked to reduced protein-protein interactions. Desolvation process can cause the protein to gradually change structure, form clumps, and eventually form nanoparticles, so might be its shows increase in entrapment efficiency. A desolvating agent volume of 4 ml resulted in a particle size of 1724 ± 1.27 nm. When the amount of desolvating agent was increased to 6 ml and 8 ml, the particle size decreased to 160 ± 0.66 nm and 218 ± 0.47 nm, respectively. Fourier Transform Infrared Spectroscopy (FTIR) data showed no incompatibilities were observed between drug and polymer. In-vitro dissolution showed the nanoparticles may follow the control release pattern over 24 hours. All the formulated batches of zeta potential were found to be in the range −30 mV to +30 mV which indicated good colloidal stability of the NPs and the PDI value ranging from 0.18 to 2.8. The higher drug encapsulation of the drug was more than 50 % which gives higher drug release at a site of action and in-vitro drug release of more than 80 % may improve the dosage frequency. The in vitro drug release data was also studied by various kinetic models. The in vitro drug release analysis shows sustained release of drug from nanoparticles and follow Korsmeyer-Peppas model. All these findings were in good agreement which may open a new gateway for future research in the field of oral oncology.