Novel surface modified solid lipid nanoparticles as intranasal carriers for ropinirole hydrochloride: application of factorial design approach

Figures & data

Table 1. 3²-Factorial design parameters, formulation composition and characterization of SLNs.

Sample code	X1 (%)	X2 (%)	Drug (mg)	Lipid (mg)	Co-surfactant (%)	Particle size (nm) (Y1)	PDI*	Zeta potential (mV) (Y2)	DL (%)	EE (%) (Y3)
L1	0.5 (−1)	0.01 (−1)	25	100	1.0	180.05 ± 4.23	0.34 ± 0.08	−16.76 ± 2.17	9.20 ± 0.34	55.23 ± 0.45
L2	1.0 (0)	0.01 (−1)	25	100	1.0	90.68 ± 3.48	0.018 ± 0.14	−19.48 ± 2.28	9.37 ± 0.27	57.16 ± 0.12
L3	1.5 (+1)	0.01 (−1)	25	100	1.0	238.20 ± 5.42	0.27 ± 0.17	−23.60 ± 3.32	9.78 ± 0.07	58.58 ± 0.32
L4	0.5 (−1)	0.05 (0)	25	100	1.0	200.18 ± 4.68	0.42 ± 0.06	30.58 ± 2.19	9.62 ± 0.64	60.78 ± 0.26
L5	1.0 (0)	0.05 (0)	25	100	1.0	66.22 ± 6.22	0.023 ± 0.21	28.19 ± 3.02	10.19 ± 0.71	61.90 ± 0.18
L6	1.5 (+1)	0.05 (0)	25	100	1.0	247.98 ± 6.78	0.234 ± 0.18	26.25 ± 4.76	10.46 ± 1.03	62.70 ± 0.46
L7	0.5 (−1)	0.1 (+1)	25	100	1.0	215.60 ± 4.93	0.034 ± 0.06	47.13 ± 1.19	10.22 ± 0.82	63.06 ± 0.17
L8	1.0 (0)	0.1 (+1)	25	100	1.0	117.00 ± 2.88	0.016 ± 0.06	42.66 ± 3.46	10.62 ± 0.14	64.10 ± 0.37
L9	1.5 (+1)	0.1 (+1)	25	100	1.0	271.61 ± 4.26	0.460 ± 0.16	37.17 ± 4.22	10.68 ± 0.29	64.73 ± 0.34

X₁ = Pluronic F-68 concentration; X₂ = stearylamine concentration; PDI = polydispersity index; DL = drug loading, EE = entrapment efficiency; +1 (High), 0 (Medium) and −1 (Low): levels used – actual and coded.

Table 2.  Summary of results of regression analysis for measured responses.

Responses	Model	R^2	Adjusted R^2	Predicted R^2	SD	%CV
Y1	Quadratic	0.8405	0.6811	−0.2045	40.09	25.53
Y2	Linear	0.8595	0.8313	0.7643	10.41	54.18
Y3	Linear	0.8939	0.8727	0.8088	1.62	2.64

Y₁: Particle size; Y₂: zeta potential; Y₃: entrapment efficiency; R²: coefficient of regression; SD = standard deviation; CV = coefficient of variation.

Table 3. Summary of results of ANOVA for measured responses.

Parameters	SS	DF	MS	F value	p Value	Significance
Particle size
Model	76229.82	9	8469.98	5.27	< 0.0105	Significant
Residual	14462.61	9	01606.96	–	–
Total	90692.43	18	–	–	–
Zeta potential
Model	9947.49	3	3315.83	30.57	< 0.0001	Significant
Residual	1626.74	15	108.45	–	–
Total	11574.23	18	–	–	–
EE
Model	331.38	3	11o.46	42.13	< 0.0001	Significant
Residual	39.33	15	2.62	–	–
Total	370.71	18	–	–	–

SS = Sum of squares; DF = degrees of freedom; MS = mean sum of squares; F = Fischer’s ratio.

Figure 1.  Response surface plots showing influence of Pluronic F-68 concentration (X₁) and stearylamine concentration (X₂) on particle size (Y₁), zeta potential (Y₂) and entrapment efficiency (Y₃).

Figure 2.  SEM photomicrograph of drug-loaded SLN formulation.

Figure 3.  Light photomicrograph of sheep nasal mucosa, untreated control mucosa (a) and drug-loaded SLN formulation treated mucosa (b).

Figure 4.  DSC thermogram of pure drug (a), lipid–drug physical mixture (b) and lyophilized sample of SLN formulation (c).

Figure 5.  In vitro (a) and ex vivo (b) drug release profiles of drug-loaded SLN formulation.

Table 4. Stability characteristics of lyophilized SLN sample (L5).

Stability parameter	0 Month	Test period 1 Month	2 Month	3 Month
Particle size (nm)	66.22 ± 6.22	74.22 ± 5.37	84.27 ± 6.12	96.62 ± 6.70
PDI	0.023 ± 0.21	0.278 ± 0.08	0.311 ± 0.06	0.238 ± 0.11
EE (%)	61.90 ± 0.18	54.16 ± 0.10	48.48 ± 0.18	41.37 ± 0.17

Values are expressed as mean ± SD, (n = 3).

Table 5. Evaluation of anti-tremor activity in mice.

Experimental groups	Time (min)
	10	20	30	40	50	60
Toxicant^a	3 ± 0.00	3 ± 0.00	3 ± 0.00	3 ± 0.00	3 ± 0.00	3 ± 0.577
Control^b	0 ± 0.00	0 ± 0.00	0 ± 0.00	0 ± 0.00	0 ± 0.00	0 ± 0.00
Standard^c	3 ± 0.00	3 ± 0.577	2 ± 0.00	1 ± 0.577	1 ± 0.00	0 ± 0.00
Formulation^d	3 ± 0.00	2 ± 0.00	1 ± 0.577	0 ± 0.00	0 ± 0.00	0 ± 0.00

Values are expressed as mean ± SEM, (n = 3);

p < 0.05 for Standard versus Toxicant and p < 0.01 for Formulation versus Toxicant.

^aInducer administration; ^bvehicle (0.9% saline solution) administration; ^cmarketed formulation administration; ^dlyophilized SLN formulation administration.