Formulation, characterization and in-vitro evaluation of self-nanoemulsifying drug delivery system containing rhamnolipid biosurfactant
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Formulation, characterization and in-vitro evaluation of self-nanoemulsifying drug delivery system containing rhamnolipid biosurfactant. / Khan, Muhammad Ahsan; Ullah, Kaleem; Rahman, Nisar ur; Mahmood, Arshad; Müllertz, Anette; Mannan, Abdul; Murtaza, Ghulam; Khan, Shujaat Ali.
In: Journal of Drug Delivery Science and Technology, Vol. 75, 103673, 2022.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - Formulation, characterization and in-vitro evaluation of self-nanoemulsifying drug delivery system containing rhamnolipid biosurfactant
AU - Khan, Muhammad Ahsan
AU - Ullah, Kaleem
AU - Rahman, Nisar ur
AU - Mahmood, Arshad
AU - Müllertz, Anette
AU - Mannan, Abdul
AU - Murtaza, Ghulam
AU - Khan, Shujaat Ali
N1 - Publisher Copyright: © 2022 Elsevier B.V.
PY - 2022
Y1 - 2022
N2 - 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. 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.
AB - 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. 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.
KW - Cryogenic transmission electron microscopy
KW - Cytotoxicity study
KW - Design of experiment
KW - In-vitro lipolysis
KW - Rhamnolipid
KW - Self-nanoemulsifying drug delivery system
U2 - 10.1016/j.jddst.2022.103673
DO - 10.1016/j.jddst.2022.103673
M3 - Journal article
AN - SCOPUS:85135947315
VL - 75
JO - Journal of Drug Delivery Science and Technology
JF - Journal of Drug Delivery Science and Technology
SN - 1773-2247
M1 - 103673
ER -
ID: 318195408