Solid lipid nanoparticles with enteric coating for improving stability, palatability, and oral bioavailability of enrofloxacin

Figures & data

Figure 1 The production process of enrofloxacin enteric granules containing SLNs inner core.

Abbreviations: ENR-SLNs, enrofloxacin-loaded SLNs; RT, room temperature; SLNs, solid lipid nanoparticles.

Table 1 Factors and levels of the L9 (3⁴) orthogonal design

Variables	Level
	1	2	3
Type	PVA	PVPK30	Poloxamer 188
Concentration	1%	2%	3%
Volume (mL)	10	15	20

Abbreviations: PVA, polyvinyl alcohol; PVP_K30, polyvinyl pyrrolidone K30.

Table 2 The optimization of emulsifier by orthogonal experiment

Sample	Type	Concentration	Volume	LC (%)	Size (µm)	Zeta potential	PDI
1	1	3	2	14.74±0.59	0.458±0.003	−20.8	0.229±0.007
2	3	3	3	12.49±0.45	1.701±0.030	−43.2	>0.5
3	1	2	3	15.66±0.25	0.459±0.004	−24.2	0.155±0.030
4	1	1	1	14.65±0.41	0.871±0.050	−29.9	>0.5
5	3	1	2	12.46±0.28	2.416±0.001	−33.1	>0.5
6	2	1	3	8.66±0.37	2.097±0.002	−29.8	>0.5
7	2	3	1	13.34±0.45	7.875±0.004	−28.5	>0.5
8	2	2	2	8.48±0.36	5.566±0.004	−32.4	>0.5
9	3	2	1	11.78±0.32	2.459±0.003	−23.2	>0.5
K1	14.99±0.65	11.89±2.47	13.23±1.20
K2	10.16±2.29	11.97±2.95	11.89±2.62
K3	12.24±0.48	13.52±1.06	12.27±2.89
R	2.75	1.63	1.34
Optimum	A1	B3	C1

Notes: K1, K2, and K3 are the average of grade of LC for three levels in each factor; R is the different value between the max and mix of K1, K2, and K3 in each level.

Abbreviations: LC, loading capacity; PDI, polydispersion index.

Figure 2 Scanning electron microscopy photographs of enrofloxacin-loaded SLNs.

Abbreviation: SLNs, solid lipid nanoparticles.

Figure 3 The accumulation release profiles of SLNs and granules in the simulated SGF (pH=2) (n=3).

Abbreviations: EC, ethyl cellulose; ENR, enrofloxacin; ENR-SLNs, enrofloxacin-loaded SLNs; PR, polyacrylic resin; SGF, simulated gastric fluid; SLNs, solid lipid nanoparticles.

Figure 4 The accumulation release profiles of SLNs and granules in the simulated SIF (pH=8) (n=3).

Abbreviations: ENR, enrofloxacin; ENR-SLNs, enrofloxacin-loaded SLNs; PR, polyacrylic resin; SIF, simulated intestine fluid; SLNs, solid lipid nanoparticles.

Table 3 The daily feed intake of pigs (mean ± SD, n=3)

Groups	Before experiment (kg/group)				During experiment (kg/group)
	1 day	2 days	3 days	$\overline{\mathrm{x}}\pm \text{SD}$	1 day	2 days	3 days	4 days	5 days	$\overline{\mathrm{x}}\pm \text{SD}$
Control	1.55	1.60	1.42	1.52±0.09	1.55	1.60	1.62	1.70	1.54	1.60±0.06
Enrofloxacin	1.44	1.59	1.62	1.55±0.09	0.11	0.19	0.15	0.17	0.12	0.15±0.03a
Simple coating	1.56	1.57	1.58	1.57±0.01	0.76	1.08	1.22	1.22	1.01	1.06±0.08a,b
10% Granules	1.41	1.45	1.58	1.48±0.08	1.15	1.22	1.56	1.46	1.74	1.43±0.24b,c
15% Granules	1.60	1.54	1.58	1.57±0.03	1.49	1.52	1.80	1.68	1.89	1.67±0.17b,d

Notes: Control group was addition feed only; 10% granules was 10% sucrose included in granules; and 15% granules was 15% sucrose included in granules.

a Statistical significance compared with control is P<0.01.

b Statistical significance compared with feed mix ENR is P<0.01.

c Statistical significance compared with simple coating is P<0.05.

d Statistical significance compared with simple coating is P<0.01.

Abbreviation: ENR, enrofloxacin.

Table 4 The influence factor test of granules (mean ± SD, n=3)

Groups	Factors	Content (%)			Unqualified granularity (%)
		0th day	5th day	10th day	0th day	5th day	10th day
Enrofloxacin granules	High light	96.0	81.6±1.13	76.8±2.12	/	/	/
	High light	10.05	9.56±2.55	9.45±1.18	7.56±0.13	7.76±0.11	7.73±0.14
	High temperature 60°C	10.05	9.97±3.10	9.23±3.56	7.87±0.09	7.73±0.15	7.83±0.11
	High temperature 40°C	10.05	9.86±2.31	9.54±1.34	7.33±0.20	7.32±0.08	7.02±0.18
	High humility	10.05	9.57±1.69	9.35±2.10	6.89±0.15	7.05±0.21	7.23±0.16

Figure 5 The influence of influencing factors experiments to release ability of enteric granules (n=3).

Notes: (A) The influence of high temperature to release ability of enteric granules. (B) The influence of high humidity to release ability of enteric granules. (C) The influence of high light to release ability of enteric granules. HT: high temperature (40°C); HI: high humidity (25°C, 90%±5%); HL: high light (4,500±500 lx).

Table 5 Pharmacokinetic parameters for ENR after oral administration of ENR enteric granules and ENR soluble powder in pigs (mean ± SD, n=6)

Parameter	Unit	Enteric granules	Soluble powder
Vd	mL/kg	3,671.07±768.5a	5,116.35±1,471.56
MRT	h	17.97±4.01b	6.80±2.28
AUC0–last	µg h/mL	11.24±3.33c	4.26±0.85
T1/2β	h	12.59±3.53d	4.71±1.58
CL	L/h/kg	240.19±62.76	579.86±130.84
Tmax	h	3.33±1.03	1.12±0.44
Cmax	µg/mL	0.52±0.05	0.60±0.12
F (%)	/	263.85%	/

Note:

a,b,c,d Statistical significance compared with soluble powder is P<0.01.

Abbreviations: AUC_0–last, area under the curve; CL, body clearance; C_max, maximum plasma concentration; ENR, enrofloxacin; F, relative bioavailability; MRT, mean residence time; T_1/2β, elimination half-life; T_max, time to reach the C_max.

Figure 6 The plasma enrofloxacin concentration profiles – time of the prepared granules and reference formulation (soluble powder) in pigs (n=6).

Notes: Granules: 10% enrofloxacin enteric granules; powder: 5% enrofloxacin soluble powder.

Figure 7 The transfer process of enrofloxacin granules in gastrointestinal tract of pigs.

Abbreviations: ENR-SLNs, enrofloxacin-loaded SLNs; SLNs, solid lipid nanoparticles.

ChunMKChoiHKPreparation and characterization of enrofloxacin/carbopol complex in aqueous solutionArch Pharm Res200427667067515283471

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