Cefquinome Sulfate Oily Nanosuspension Designed for Improving its Bioavailability in the Treatment of Veterinary Infections

Figures & data

Table 1 Effects of Different Preparation Methods on Particle Size and PDI of CS-NSP, n=3, mean ±SD

Method	0 h		48 h
	Particle Size (nm)	PDI	Particle Size (nm)	PDI
Medium grinding	2483.61±92.688**	10.882±8.08**	3054.20±164.25**	15.62±9.23**
Mortar grinding	725.15±79.19*	0.782±0.42*	819.66±84.74**	2.769±2.40*
CS-INJ	1136.29±29.06	0.884±0.46	1756.09±182.85	2.197±1.18

Notes: *p<0.05, formula made by medium grinding or mortar grinding compared with CS-INJ; **p<0.01, formula made by medium grinding or mortar grinding compared with CS-INJ.

Figure 1 (A) Effect of stabilizer types, (B) Labrasol concentration, (C) glycerol monostearate concentration, (D) Labrafil M 1944 CS concentration (E) grinding time, and (F) dilution multiple on particle size and PDI of CS-NSP, respectively. n=3, mean ±SD.

Table 2 Process Validation Results, n=3, mean ±SD

Batches	Particle Size (nm)	PDI	Average Particle Size (nm)	Average PDI
1	739.61±82.78	0.806±0.52	772.70±82.03	0.828±0.45
2	785.39±89.19	0.822±0.38
3	796.09±74.11	0.856±0.46

Table 3 Comparison of Viscosity and Content Determination Between CS-NSP and CS-INJ with the Same Concentration in the Market, n=3, mean ±SD

Marked Concentration (mg/mL)	Determination	Sample	Results (%)
25	Content	CS-NSP	104.2±5.3
		CS-INJ	96.7±2.35
	Viscosity	CS-NSP	13.13±0.63*
		CS-INJ	54.90±1.89

Notes: *p<0.01, CS-NSP compared with CS-INJ.

Table 4 Pharmacokinetic Parameters in Rats After Intramuscular Administration of CS-INJ and CS-NSP at a Dosage of 40 mg CS/kg Body Weight, n=5, mean ±SD

Parameters	Units	CS-INJ	CS-NSP
t1/2	H	1.42±0.36	1.86±0.97
Tmax	H	0.48±0.17	0.65±0.22
Cmax	μg/mL	32.23±7.71	62.88±12.54**
AUC0-t	μg/mL*h	64.02±13.08	115.94±22.21**
AUC0-∞	μg/mL*h	66.03±13.35	118.69±21.73**
AUMC0-∞	μg/mL*h^2	141.80±50.28	216.32±58.49
MRT	H	2.12±0.56	1.81±0.38
V	L/kg	0.35±0.09	0.29±0.17
CL	L/h/kg	0.17±0.03	0.11±0.02*

Notes: *p<0.05, CS-NSP compared with CS-INJ; **p<0.01, CS-NSP compared with CS-INJ.

Figure 2 (A) Transmission electron microscopy of CS-NSP. (B) Appearance of CS-NSP and CS-INJ. (C) Particle size distribution of CS-NSP and (D) CS-INJ.

Figure 3 (A) Crystallize cefquinome sulfate in CS-NSP and CS-INJ to obtain solid powders and compare them with API for infrared analysis. (B) CS-NSP, CS-INJ and the physical mixture without bulk drug in liquid station for differential calorimetry and thermogravimetric analysis. (C) Crystallize cefquinome sulfate in CS-NSP and CS-INJ to obtain solid powders and compare them with API for X-ray diffraction.

Figure 4 The comparison of cumulative release percentage profiles in CS-NSP and CS-INJ.

Figure 5 (A) Comparison of sedimentation volume ratio of CS-INJ and CS-NSP. (B) The change trend at illuminated light 4500 lx, (C) relative humidity 92%, and (D) temperature 60°C, on particle size and PDI of CS-NSP. (E) The change trend in Groups 1, 2, and 3 on content. (F) The change trend at illuminated light 4500 lx, (G) relative humidity 92%, and (H) temperature 60°C, on in cumulative release percentage profiles of CS-NSP, n=3, mean±SD.

Figure 6 (A) Comparison of hemolysis rate of CS-NSP and CS-INJ. (B) Appearance of red blood cell suspension with (1–4) CS-NSP, (5–8) CS-INJ, (9) negative control, and (10) positive control after centrifugation, respectively.

Figure 7 H&E staining image at the injection site of (1) normal saline group, (2) 0.2 mL Labrafac PG group, (3) 0.2 mL CS-NSP group, (4) 0.1 mL CS-NSP group, and (5) 0.2 mL CS-INJ, respectively.

Figure 8 The mean plasma concentration – time profiles of CS-NSP and CS-INJ. Each rat was administrated at a dosage of 40 mg/kg body weight via intramuscular injection, and blood samples were collected at 0.17, 0.33, 0.50, 0.75, 1, 1.5, 2.5, 3.5, 4.5, 6, and 8.5 h, n=5, mean ±SD. *p<0.05, CS-NSP compared with CS-INJ; **p<0.01, CS-NSP compared with CS-INJ.