Optimization of nanostructured lipid carriers for topical delivery of nimesulide using Box–Behnken design approach

Figures & data

Table 1. Variables in Box–Behnken design to form nimesulide-loaded NLC formulations.

Variables	Levels
	−1	0	+1
Independent variables
X1 = Stearic acid: oleic acid	7:3	8:2	9:1
X2 = Poloxamer 188 (%w/w)	1.0	1.5	2.0
X3 = Lecithin (%w/w)	0.5	1.0	1.5
Dependent variables			Constraints
Y1 = Particle size (nm)			Minimize
Y2 = Entrapment efficiency (%)			Maximize

Figure 1. Solubility of nimesulide in different oils (A) and amount of different lipids required to solubilized nimesulide (B).

Table 2. Observed response in the Box–Behnken design for nimesulide NLC formulations (mean ± SD).

Formulation code	Independent variables			Dependent variables		Poly dispersity index^a	Flux (μg/cm^2/h)^a
	X1	X2	X3	Y1	Y2
F1	9:1	1.5	0.5	488.51 ± 92	60.5 ± 2.11	0.458 ± 0.012	0.98 ± 0.11
F2	9:1	1.0	1.0	499.80 ± 12	65.5 ± 0.99	0.451 ± 0.008	0.95 ± 0.14
F3	8:2	1.5	1.0	285.51 ± 15	76.7 ± 1.71	0.411 ± 0.062	1.68 ± 0.08
F4	8:2	2.0	0.5	293.1 ± 10	70.3 ± 1.32	0.434 ± 0.051	1.63 ± 0.09
F5	8:2	1.0	1.5	275.5 ± 9	80.5 ± 0.99	0.362 ± 0.034	1.83 ± 0.12
F6	7:3	2.0	1.0	196.8 ± 18	82.6 ± 1.54	0.351 ± 0.032	2.54 ± 0.09
F7	9:1	2.0	1.0	470.4 ± 7	61.3 ± 2.50	0.442 ± 0.029	1.16 ± 0.10
F8	8:2	1.0	0.5	305.1 ± 17	76.5 ± 0.98	0.428 ± 0.044	1.51 ± 0.11
F9	7:3	1.5	1.5	214.4 ± 11	89.4 ± 3.40	0.335 ± 0.018	2.66 ± 0.09
F10	9:1	1.5	1.5	456.7 ± 13	68.1 ± 1.76	0.407 ± 0.061	1.36 ± 0.08
F11	7:3	1.5	0.5	242.3 ± 10	83.3 ± 3.43	0.393 ± 0.052	2.18 ± 0.07
F12	8:2	2.0	1.5	247.2 ± 9	78.4 ± 1.95	0.370 ± 0.002	1.92 ± 0.09
F13	8:2	1.5	1.0	283.6 ± 14	76.3 ± 0.99	0.411 ± 0.023	1.68 ± 0.08
F14	7:3	1.0	1.0	260.6 ± 10	86.5 ± 2.62	0.371 ± 0.026	1.68 ± 0.09
F15	8:2	1.5	1.0	284.3 ± 11	76.1 ± 1.01	0.411 ± 0.031	1.68 ± 0.07

X₁ = Ratio of stearic acid: oleic acid, X₂ = Poloxamer 188 (%w/w), X₃ = Lecithin (%w/w), Y₁ = Particle size (nm), Y₂ = Entrapment efficiency (%).

a Not included in the optimization model.

Figure 2. Three-dimensional response surface plot showing effect of independent variables on nimesulide-loaded NLC (A) particle size and (B) entrapment efficiency.

Figure 3. Transmission electron micrograph of optimized nimesulide-loaded NLC (A). Particle size distribution of optimized NLC formulation-loaded with nimesulide (B).

Figure 4. Confocal laser scanning micrograph after application of Rhodamine B-loaded optimized NLC formulation (F9), optical cross-sections perpendicular to the rat skin surface.