Quality by design approach for development and characterization of solid lipid nanoparticles of chlorogenic acid

Chlorogenic acid is a polyphenol that has potent antioxidant and antidepressant activity. Chlorogenic acid is a BCS class-III category compound (high solubility and low permeability). Due to low permeability and extensive first-pass metabolism (resulting in less oral bioavailability) and poor stability of chlorogenic acid, its uses are restricted. Hence, chlorogenic acid can be encapsulated in a lipid as a successful technique for enhanced permeability and reduced first-pass metabolism, resulting in enhanced bioavailability and improved stability. The objective of the research work was the formulation and optimization of Chlorogenic acid solid lipid nanoparticles (SLNs) for improved permeability and excellent stability using a 3-factor, 5-level central composite design (CCD). Chlorogenic acid SLNs were formulated by hot emulsification and ultrasonication. Glyceryl monostearate (GMS) has been employed as a solid lipid, while Tween 80 has been employed as a surfactant. A 5-level CCD model has been used for the optimization of the chlorogenic acid SLNs and to determine the influence of independent factors (variables) on dependent or response variables. The independent variables used in the model include lipid concentration, homogenization time, and surfactant concentration. The response variables include percent entrapment efficiency (%EE), particle size, and polydispersity index (PDI). The lyophilized chlorogenic acid SLNs were considered for the stability study at “5±3 ο C/60±5% RH and 25±2 ο C/60±5% RH” for three months. The optimized formula obtained for chlorogenic acid SLNs had 1382.9 mg GMS, 3% of tween 80, and 33.5 min of homogenization time, giving the highest entrapment (68.63%). The mean particle size was 212.4 nm with PDI 0.162 and zeta potential of −14.9 mV. In-vitro release of the drug followed the Korsmeyer-Peppas kinetic model with R 2 = 0.914 and n = 0.721, demonstrating non-Fickian diffusion and better permeability of the Chlorogenic acid. Images of ‘scanning electron microscopy (SEM)’ exhibited spherical particles with smooth surfaces. “Fourier-transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction” studies determined the compatibility of chlorogenic acid with excipients. The data of the stability study exhibited 5 ο C storage temperature suitable for maintaining the significant features of nanoparticles within the acceptable range. Since SLN with acceptable qualities and prospective application for intestinal lymphatic transport were produced, the development and optimization process using Quality by Design was justified. • Chlorogenic acid-solid lipid nanoparticles (SLNs) were formulated by hot emulsification followed by ultrasonication method. • The 5-level Central Composite Design model was used for the optimization of the chlorogenic acid-SLNs. • The drug's compatibility with the excipients was confirmed by Fourier-Transform Infrared Spectroscopy, Differential Scanning Calorimetry, and X-ray Diffraction. • The morphological features of the Chlorogenic acid-SLNs were determined by Scanning Electron Microscopy. • In-vitro drug release study followed the Korsmeyer-Peppas kinetic model that confirmed non-Fickian diffusion as the release mechanism. • Stability study exhibited 5 °C storage temperature suitable for maintaining the significant features of SLNs within the acceptable range.