Sustained release ivermectin-loaded solid lipid dispersion for subcutaneous delivery: in vitro and in vivo evaluation

Figures & data

Figure 1. X-ray powder diffraction patterns of IVM-SDs, IVM-PMs, IVM, and HCO. IVM-SD, ivermectin-loaded solid dispersion; IVM-PM, physical mixtures of IVM, and HCO; IVM. native ivermectin; HCO, hydrogenated castor oil, the carrier of solid dispersion.

Figure 2. Fourier-transformed infrared spectroscopy spectra of IVM-SDs, IVM-PMs, IVM, and HCO. IVM-SD, ivermectin-loaded solid dispersion; IVM-PM, physical mixtures of IVM, and HCO; IVM, native ivermectin; HCO, hydrogenated castor oil, the carrier of solid dispersion.

Figure 3. In vitro dissolution profile of IVM-SDs, IVM-PMs, and IVM. IVM-SD, ivermectin-loaded solid dispersion; IVM-PM, physical mixtures of IVM, and HCO; IVM, native ivermectin; HCO, hydrogenated castor oil.

Figure 4. Plasma time–concentration profiles of IVM after subcutaneous administration of SD1:3 and IVM in rabbits. The inset figure was the plasma time–concentration profiles after 21 d. The results were expressed as mean ± SD (n = 4). SD1:3, ivermectin-loaded solid dispersion with drug:carrier weight ratios of 1:3; IVM, native ivermectin.

Table 1. Main pharmacokinetic parameters (mean ± SD, n = 4) of IVM after subcutaneous administration of SD1:3 and IVM in rabbits.

Parameters	IVM	SD1:3
Cmax(ng/mL)	22.25 ± 5.97	18.18 ± 8.53
Tmax (day)	1.50 ± 0.58	2.75 ± 2.87
AUCINF (ng day/mL)	255.61 ± 68.63	277.6 ± 84.91
MRT (day)	18.45 ± 4.97	30.31 ± 5.61^a

The letter “a” denotes significant differences between the SD1:3 and the IVM group (p < 0.05).

Table 2. Clinical scores of infection of rabbits and number of positive rabbits.

		Days
Groups	Efficacy criteria	0	7	14	28	42
SD1:3	Number of positive rabbits	8	2	0	0	0
	lesion scores	2.63 ± 1.30^a	0.63 ± 0.23^a	0.44 ± 0.18^ab	0.00 ± 0.00^a	0.00 ± 0.00^a
(IVOMEC)	Number of positive rabbits	8	0	1	3	5
	lesion scores	2.13 ± 1.25^a	0.44 ± 0.18^a	0.86 ± 0.94^b	1.58 ± 1.24^b	2.25 ± 0.99^b
Vehicle Control	Number of positive rabbits	5	5	5	0	0
	lesion scores	2.00 ± 0.71^a	3.20 ± 0.45^b	3.40 ± 0.55^c	0.30 ± 0.27^a	0.00 ± 0.00^a

The different letters within a column denote significant differences between the different groups (p < 0.05).