Integrating quality by design and Hansen solubility parameters in preformulation of Vanillic Acid-Loaded nanostructured lipid carriers (Part I)

Abstract

Phenolic acids such as vanillic acid (VA) possess diverse pharmacological activities, however, their clinical application is hindered by poor solubility and bioavailability. In this study, a systematic quality by design (QbD) approach was followed to develop versatile VA-loaded nanostructured lipid carriers (NLCs). First, quality target product profile (QTPP) and critical quality attributes (CQAs) were identified, followed by a risk assessment using an Ishikawa diagram and failure mode and effect analysis (FMEA). Hansen solubility parameters and experimental solubility studies identified the optimal solid and liquid lipids for solubilizing VA, at 70:30 ratio as suggested by differential scanning calorimetry (DSC) and filter paper method. Plackett-Burman design was employed to screen eleven high-risk factors, where Pareto charts and perturbation plots identified stirring time, amounts of lipid, VA and lecithin, aqueous phase volume, stabilizer type and concentration, sonication time and on: off cycles as significant factors affecting the CQAs. The prepared NLCs displayed a wide range of particle sizes (203.6 nm to 2048 nm), a negative surface charge and a high entrapment reaching 86.35 %. These characteristics make the developed NLCs adaptable for most routes of administration and provide a practical QbD framework that can guide the development of a wide range of phenolic acid-loaded NLCs.