Novel development of lipid-based formulations: Improved wettability and homogeneous API solid dispersion visualised...

Lipid-based formulations have been successfully applied to improve the aqueous solubility of active pharmaceutical ingredients (APIs), however, with the bottleneck of limited wettability of the system. In this study, a lipid-based system was developed using polyglycerol ester of fatty acids (PGFA) as the main component and hexaglycerol (PG6) as a wetting agent. Felodipine, a BCS class II compound was selected as a model API. Two different temperatures (95 °C and 55 °C) were used to produce API loaded melt-casted samples, with and without PG6. Near-infrared hyperspectral imaging (NIR-HSI) was used as an advanced tool to evaluate and optimize felodipine dispersion in the lipid-based system. The established NIR-HSI model demonstrated excellent linearity and accuracy (R²Y = 80.999, RMSEC = 0.084) and acted as a powerful tool for screening and optimizing the API dispersibility. Applying 95 °C for producing melt-casted samples enhanced the molecular distribution of felodipine, drug amorphization and uniform dispersion within the matrix. Felodipine inhibited the crystal growth of the lipid. A concentration dependent API release (first order kinetics) was observed from all lipid-based formulations. The API release rate was affected by the lipid crystalline size, the wettability of the system and the type of solid dispersion of API in the lipid-based matrix. Deep understanding of these parameters combined with the application of the novel and robust analytical tools such as NIR-HSI is necessary to pave the way of developing advanced lipid-based formulations with tailored API release.