Development, optimization, and evaluation of a nanostructured lipid carrier of sesame oil loaded with miconazole for the treatment of oral candidiasis

Figures & data

Table 1. The uncoded and coded levels of the NLC formulation factors were investigated using the face-centered central composite design.

Factor	Level
Independent variables	−1	0	+1
X1: Total lipid-to-drug ratio	10:1	15:1	20:1
X2: Oil-to-solid lipid ratio	1:4	2:4	4:4
X3: Surfactant concentration (%)	0.5	1	2
Dependent variables	Constraints
Y1: Particle size	Minimum
Y2: Dissolution efficiency (DE)	Maximum
Y3: Inhibition zone against oral candidiasis (Y3)	Maximum

Figure 1. Solubility of MZ in various lipids.

Table 2. The obtained particle size from various trials by the experimental central composite design (CCD) for the SO-based NLCs of miconazole (MZ-SO NLCs).

	Factor 1	Factor 2	Factor 3	Response 1	Response 2	Response 3
Run	A: Total lipid-to-MZ ratio	B: SO-to-compritol ratio	C: Labrasol concentration (%)	Particle size (nm)	Dissolution efficiency (%)	Inhibition zone (mm)
1	0	−1	0	270	55	9
2	0	0	0	235	59	17
3	1	1	1	95	64	22
4	1	0	0	255	39	13
5	0	0	0	206	55	18
6	0	0	0	270	57	17
7	−1	−1	1	161	70	16
8	−1	−1	−1	390	43	13
9	0	1	0	100	60	27
10	1	−1	−1	410	36	5
11	−1	1	1	92	88	29
12	1	1	−1	270	41	18
13	−1	1	−1	240	55	19
14	0	0	−1	320	44	13
15	−1	0	0	220	79	19
16	1	−1	1	167	59	13
17	0	0	1	121	71	19

Table 3. Regression analysis results for selected responses (i.e. particle size, dissolution efficiency, and inhibition zone).

Responses	R^2	Adjusted R²	Predicted R²	Coefficient of variation (%CV)	Adequate precision
Particle size	0.9008	0.8778	0.8258	14.88	17.7249
Dissolution efficiency	0.9056	0.8838	0.8232	8.50	20.0078
Inhibition zone	0.9430	0.9298	0.8935	9.25	26.1972

Figure 2. Effects of independent factors on the particle size of different prepared drug-loaded NLCs: (a) main effect plot, (b) contour plot, and (c) 3D surface plot.

Figure 3. Effects of independent factors on the dissolution of different prepared drug-loaded NLCs: (a) main effect plot, (b) contour plot, and (c) 3D surface plot.

Figure 4. Effects of independent factors of different prepared drug-loaded NLCs on the inhibition zone: (a) main effect plot, (b) contour plot, and (c) 3D surface plot.

Figure 5. The desirability ramp shows the levels of the predicted and independent values for the optimized nanoformulation responses.

Table 4. Predicted and experimental responses of the optimized nanoformulation.

Solution	Total lipid-to-MZ ratio	SO-to-compritol ratio	Labrasol (%)	Particle size (nm)	Dissolution efficiency (%)	Inhibition zone (mm)	Desirability
Predicted value	10:1	4:4	2	80.98	81.01	26.80	0.923
Experimental value	10:1	4:4	2	82	84	28	0.923

Figure 6. SEM of ultramorphological study of the optimized nanoformulation.

Table 5. Determined permeation parameters for MZ from different formulations (n = 3; mean ± SD).

Permeation Parameters	Marketed MZ cream (Daktarin 2%, Janssen, India)	Optimized MZ-SO NLC formulation	MZ aqueous suspension
Cumulative amount permeated (μg/cm^2)	1215 ± 22.27	1472 ± 20.42	470 ± 7.00
Steady state flux, Jss, (μg/cm^2.min)	4.31 ± 0.15	5.61 ± 0.18	2.00 ± 0.17
Permeability coefficient, P, (cm/min)	1.01 ± 0.04 × 10^−4	1.32 ± 0.13 × 10^−4	0.51 ± 0.02 × 10^−4
Diffusion coefficient, D, (cm^2/min)	28.6 ± 3.25 × 10^−5	37.2 ± 2.00 × 10^−5	6.62 ± 0.77 × 10^−5
Relative permeation rate (RPR)		1.21 ± 0.20	0.39 ± 0.03
Enhancement factor (Fen)	2.59 ± 0.14	3.13 ± 0.21

Table 6. Ulcer index values of different animal groups (mean ± SD, n = 6).

Animal group	Ulcer index
optimized 2% MZ-SO NLC	0.5 ± 0.50
SO alone	1.5 ± 0.25
Commercially available 2% MZ marketed oral gel	2.5 ± 0.25
Normal saline	4 ± 0.5

Data availability statement

Data used to support the findings of this study are included within the article.