Design and optimization of curcumin loaded nano lipid carrier system using Box-Behnken design

Herbal antioxidant like curcumin holds great potential to treat neurodegenerative disease like Alzheimer’s disease. However, its therapeutic potency is obstructed due to rapid metabolism, poor solubility, GI susceptibility, enzymatic degradation and lower bioavailability. Thus, the present work aimed to design and optimize curcumin-loaded NLC (CNL) with higher drug entrapment, prolonged release and better stability. CNL was prepared by modified melt emulsification method followed by ultrasonication.

Highlights

Imperfect lattice structure of NLC greatly enhances drug entrapment efficiency.

Drug loaded NLC was prepared by melt-emulsification ultrasonication method.

Effect of solid: liquid lipid, surfactant concentration on formulation was optimized.

Initial burst release with subsequent sustained release of 92.73% drug.

Weibull kinetic exponent showed combined release mechanism with Fickian diffusion.

The formulation was optimized by 3 factor 3 level Box-Behnken design using solid: liquid lipid, surfactant concentration and ultrasonication time as independent variable while particle size, entrapment efficiency and % drug release as dependant variable. The design suggested 3.092 solid:liquid lipid, 2.131% surfactant and 4.757 min ultrasonication fit best to get the optimized formulation. The size of the optimized CNL was noted 124.37 ± 55.81 nm, which is in the acceptable range for brain delivery. SEM results also comply with this size range (near 150 nm) and demonstrated almost spherical and uniform particles with porous and uneven surface structures. PDI, zeta potential, entrapment efficiency and % drug release were observed as 0.201 ± 0.00, − 17.2 ± 2.35 mV, 93.62 ± 0.68% and 92.73 ± 0.06%, respectively.

The NLC demonstrated initial burst release with subsequent prolonged release of drug for 48 h. Weibull kinetic equation with 0.9958 R², minimum AIC and maximum MSC value was found best fit to explain the release behavior. The β exponent and diffusional coefficient (n) indicated combined release mechanism with Fickian diffusion as drug release mechanism. Formulation was also found stable at different storage condition.

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Materials: Curcumin (Cur, 98%) was kind gift from the Department of Pharmaceutics, Ramanbhai Patel College of Pharmacy (RPCP), CHARUSAT, (Gujarat, India). Glyceryl behenate (Compritol® 888), Glyceryl distearate (Precirol® ATO 5) were provided as gift sample from Gattefosse SAS, France. Glyceryl monostearate (GMS), Glyceryl tristearate (Dynasan® 118), Glyceryl trimyristate (Dynasan® 114), Oleic acid (OA), Triglycerides of capric/caprylic acid (Captex® 300 and Captex® 355), Phospholipon® 80H (70%, soy phosphatidylcholine), Tween 80 and other excipients were also gifted from Department of Pharmaceutics, Ramanbhai Patel College of Pharmacy (RPCP), CHARUSAT, (Gujarat, India). All the other reagents, solvents, and chemicals used in the experiment were of analytical grade.

Article information: Mukta Agrawal, Shailendra Saraf, Madhulika Pradhan, Ravish J. Patel, Gautam Singhvi, Ajazuddin, Amit Alexander. Design and optimization of curcumin loaded nano lipid carrier system using Box-Behnken design, Biomedicine & Pharmacotherapy, Volume 141, 2021. https://doi.org/10.1016/j.biopha.2021.111919.