Formulation, characterization and in-vitro evaluation of self-nanoemulsifying drug delivery system containing rhamnolipid biosurfactant

Self-nanoemulsifying drug delivery systems (SNEDDS) are most commonly used lipid-based drug delivery systems for bioavailability enhancement. Mostly SNEDDS contains high concentrations of synthetic surfactants which may result in gastric irritation and cause toxicity. In this study, Rhamnolipid, a biosurfactant, is utilized as a cosurfactant to minimize the quantity of synthetic surfactant in SNEDDS formulation. Two sets of SNEDDS formulations comprising of medium-chain (MC) or long-chain (LC) glycerides, Kolliphor ® RH40 (KOL) and Rhamnolipid (RL) were produced using a D-optimal design in MODDE software. The monodispersed SNEDDS preconcentrates were further characterized by utilizing dynamic light scattering (at pH 2.5 & 6.5), cryogenic transmission electron microscopy, thermodynamic stability, in-vitro lipid digestion, and viscosity measurements.

Highlights

• Long chain-SNEDDS containing rhamnolipid (LC-SNEDDS-RL) produced nanoemulsions with droplet sizes ranging from 21 to 336 nm.

• The LC-SNEDDS-RL showed reduction in droplet sizes when dispersed in simulated intestinal media while droplet size slightly increased in simulated gastric fluid which suggested that rhamnolipid reduce droplet size more efficiently at higher pH.

• The zeta potential of nanoemulsion produced by dispersion of LC-SNEDDS-RL was decreased at low pH.

• The LC-SNEDDS-RL formulations were thermodynamically stable and showed non-Newtonian properties and suitable for capsule filling process.

• During cytotoxicity studies, the LC-SNEDDS-RL were well-tolerable at doses normally administered to human.

• In conclusion, this study demonstrated that long chain-SNEDDS comprising of rhamnolipid as cosurfactant are favorable formulations when reduction in amount of synthetic surfactant is desirable and rhamnolipid also possibly helps to alter the digestion rate.

All MC-SNEDDS preconcentrates were not homogenous and considered unstable, while LC-SNEDDS were homogenous and produced nanoemulsions with droplet sizes ranging from 21 to 336 nm. LC-SNEDDS formulations containing RL produced smaller droplet sizes when dispersed in simulated intestinal media while droplet size slightly increased in the simulated gastric fluid which suggested that RL reduces droplet size more efficiently at higher pH. The zeta potential of nanoemulsion produced by dispersion of LC-SNEDDS containing RL was decreased at low pH.

Thermodynamic stability studies have shown that all selected preconcentrates were stable. During in vitro lipolysis, only 24–34% of formulations were enzymatically digested, and at higher concentrations of RL, low number of fatty acids was released. Based on the results of dynamic viscosity studies, all the formulations showed non-Newtonian properties and were suitable for the capsule filling process. During cytotoxicity studies, LC-SNEDDS formulation and RL cosurfactant were well-tolerable at doses normally administered to human. In conclusion, this study demonstrated that LC-SNEDDS comprising RL as cosurfactant are favorable formulations when reduction in the amount of synthetic surfactant is desirable and RL also possibly helps to alter the digestion rate.

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Muhammad Ahsan Khan, Kaleem Ullah, Nisar ur Rahman, Arshad Mehmood, Anette Müllertz, Abdul Mannan, Ghulam Murtaza, Shujaat Ali Khan,
Formulation, characterization and in-vitro evaluation of self-nanoemulsifying drug delivery system containing rhamnolipid biosurfactant, Journal of Drug Delivery Science and Technology, 2022, 103673, ISSN 1773-2247,
https://doi.org/10.1016/j.jddst.2022.103673.