Modeling, Designing and Evaluating Fully Dilutable Self Microemulsifying Delivery System for Hydrophobic Pharmaceuticals and Nutraceuticals

Many newly discovered drugs and nutraceuticals are hydrophobic in nature. When these drugs and nutraceuticals are ingested, their low aqueous solubility limits their ability to dissolve in intestinal fluid and eventually permeate the intestinal membrane to become bioavailable. To overcome this limitation, various delivery systems have been developed to enhance the solubility and absorption of active ingredients. Lipid-based delivery systems (LBDS) such as microemulsions (μE) and self-microemulsifying delivery systems (SMEDS) are among the most advanced systems. However, there are multiple technological challenges in the design and applications of SMEDS. Using lecithin as the main surfactant and hydrophilic and lipophilic linkers as co-surfactants, a platform was developed to produce food-grade, fully dilutable microemulsions containing hydrophobic solutes. The in vitro and in vivo experiments showed a high solubilization capacity for hydrophobic solutes. For ibuprofen, used as a model solute a significant improvement in absorption and bioavailability was observed. The results also showed a shorter absorption time and a longer drug circulation time when ibuprofen was formulated in fully dilutable system. The main tool used to design the fully dilutable SMEDS was the hydrophilic-Lipophilic –Difference (HLD) framework. HLS was used to predict the phase inversion point of surfactant-oil-water (SOW) systems as a function of formulation composition. The HLS was further coupled with Net-Average0Curveture (NAC) model to predict the minimum surfactant required to produce fully dilutable systems. The same tool was also used to characterize the effect of the solute on the formulation and design reformulation strategies to maintain the fully dilutable path. To explore the potential for controlled release with SMEDS, the idea of integrating the concepts of SMEDS and organogels was explored. This novel self-dispersing organogel provides 1-4 days release, which is a substantial improvement over the improved release obtained with SMEDS alone.Ph.D.2021-04-30 00:00:0