Impact of emulsion-based drug delivery systems on intestinal permeability and drug release kinetics

Lipid based drug delivery systems, and in particular self-emulsifying drug delivery systems (SEDDS), show great potential for enhancing oral bioavailability but have not been broadly applied, largely due to lack of general formulation guidance. To help understand how formulation design influences physicochemical emulsion properties and associated function in the gastrointestinal environment, a range of twenty-seven representative self-emulsifying formulations were investigated. Two key functions of emulsion-based drug delivery systems, permeability enhancement and drug release, were studied and statistically related to three formulation properties — oil structure, surfactant hydrophilic liphophilic balance (HLB) values, and surfactant-to-oil ratio. Three surfactants with HLB values ranging from 10 to 15 and three structurally different oils (long chain triglyceride, medium chain triglyceride, and propylene glycol dicaprylate/dicaprate) were combined at three different weight ratios (1:1, 5:1, 9:1). Unstable formulations of low HLB surfactant (HLB = 10) had a toxic effect on cells at high (1:1) surfactant concentrations, indicating the importance of formulation stability for minimizing toxicity. Results also indicate that high HLB surfactant (Tween 80) loosens tight junction at high (1:1) surfactant concentrations. Release coefficients for each emulsion system were calculated. Incorporation of a long chain triglyceride (Soybean oil) as the oil phase increased the drug release rate constant. These results help establish an initial foundation for relating emulsion function to formulation design and enabling bioavailability optimization across a broad, representative range of SEDDS formulations.

Formulations of low HLB surfactant, which also did not form uniform emulsions, showed toxic effect on intestinal cells implying that emulsion stability might be an important factor in maintaining viability. Figure optionsDownload as PowerPoint slide