Preparation, Characterization and Pharmacokinetics of Liposomes-Encapsulated Cyclodextrins Inclusion Complexes for Hydrophobic Drugs

Figures & data

FIG. 1 Phase solubility diagrams for indomethacin with increasing concentrations of β -CD and HP-β -CD.

FIG. 2 DTA thermograms of (A) indomethacin (IMC), (B) β -CD, (C) HP-β -CD, (D) IMC + β -CD (physical mixture), (E) IMC+HP-β -CD (physical mixture), (F) IMC/β -CD inclusion complexes, and (G) IMC/HP-β -CD inclusion complexes.

FIG. 3 Release profiles of liposomes-encapsulated IMC (▴), IMC/β -CD inclusion complexes (□), and IMC/HP-β -CD inclusion complexes (•) in phosphate buffer saline (pH 7.4). Results are expressed as means ± S.D. of four determinations.

FIG. 4 Mean serum concentration-time profiles in rabbits for liposomes-encapsulated IMC (▴), and IMC/β -CD inclusion complexes (□), and IMC/HP-β -CD inclusion complexes (•) after intravenous administration. The vertical bars represent the standard error of mean (n = 4).

FIG. 5 Mean serum concentration-time profiles in rabbits for liposomes-encapsulated IMC (▴), IMC/β -CD inclusion complexes (□), and IMC/HP-β -CD inclusion complexes (•) after intramuscular administration. The vertical bars represent the standard error of mean (n = 4).

TABLE 1 Pharmacokinetic parameters of liposomes-encapsulated IMC, IMC/β -CD inclusion complexes, and IMC/HP-β -CD inclusion complexes after intravenous administration

Parameters	IMC	IMC/β -CD	IMC/HP-β -CD
A (μg · ml^− 1)	25.69 ± 20.00	17.52 ± 8.65	17.60 ± 8.20
α (min^−1)	0.18 ± 0.10	0.12 ± 0.05	0.18 ± 0.16
B (μg · ml^− 1)	2.42 ± 0.53	2.79 ± 0.52	2.99 ± 1.24
β (min^−1)	0.0094 ± 0.0017	0.0066 ± 0.0007	0.0068 ± 0.0033
t1/2α(min)	4.6 ± 1.8	6.6 ± 2.6	6.0 ± 3.0
t1/2β(min)	75.4 ± 13.6	106.8 ± 11.8	122.7 ± 63.1
AUC (μg · min · ml^−1)	390.4 ± 23.4	580.8 ± 50.9	629.0 ± 150.7

TABLE 2 Pharmacokinetic parameters of liposomes-encapsulated IMC, IMC/β -CD inclusion complexes, and IMC/HP-β -CD inclusion complexes after intramuacular administration

Parameters	IMC	IMC/β -CD	IMC/HP-β -CD
A (μg · ml^− 1)	2.82 ± 0.96	5.97 ± 1.34	7.00 ± 1.33
ke(min^−1)	0.0090 ± 0.0028	0.0106 ± 0.0017	0.0118 ± 0.0040
ka(min^−1)	0.43 ± 0.26	0.46 ± 0.16	0.37 ± 0.10
t1/2ka(min)	2.06 ± 1.11	1.62 ± 0.47	1.98 ± 0.48
t1/2ke(min)	83.18 ± 27.19	67.18 ± 13.07	63.34 ± 19.72
Tmax(min)	10.59 ± 3.77	8.87 ± 2.25	10.06 ± 2.08
Cmax(μ g · ml^− 1)	2.43 ± 0.69	5.21 ± 1.14	6.02 ± 1.22
AUC (μg · min · ml^−1)	356 ± 31	782 ± 130	793 ± 123