Nanotransfersomes-loaded thermosensitive in situ gel as a rectal delivery system of tizanidine HCl: preparation, in vitro and in vivo performance

Figures & data

Table 1. Composition, entrapment efficiency, vesicle diameter and ex vivo permeation parameters of TIZ-loaded nanotransfersomes.

Formula	EA used	Composition (PC:EA)	EE (%)	Vesicle diameter (nm)	Q24h (μg/cm)	J (μg/cm^2 h)	Lag time (min)	Kp (cm/h)
F1	Span 80	95:5	60.16 ± 1.59	253.97 ± 6.6	198.36 ± 3.55	8.27 ± 0.15	30 ± 3.14	0.004469 ± 0.0007
F2	Span 80	85:15	56.74 ± 0.97	237.66 ± 7.1	222.80 ± 4.19	9.28 ± 0.18	23 ± 1.08	0.004873 ± 0.0009
F3	Span 80	75:25	58.83 ± 1.74	191.90 ± 3.5	166.19 ± 2.89	6.92 ± 0.13	24 ± 1.43	0.003899 ± 0.0008
F4	Tween 80	95:5	55.63 ± 2.04	198.87 ± 2.3	280.71 ± 2.20	11.69 ± 0.09	28 ± 2.13	0.01624 ± 0.0039
F5	Tween 80	85:15	52.39 ± 1.13	150.33 ± 2.8	411.49 ± 5.33	17.15 ± 0.22	11 ± 1.99	0.03628 ± 0.0078
F6	Tween 80	75:25	45.80 ± 1.55	145.03 ± 3.6	329.69 ± 4.71	13.74 ± 0.19	13 ± 3.60	0.01764 ± 0.0112
F7	Brij 35	95:5	43.21 ± 2.33	175.47 ± 1.1	324.67 ± 4.58	13.53 ± 0.19	15 ± 2.78	0.02668 ± 0.0130
F8	Brij 35	85:15	42.83 ± 1.45	149.73 ± 1.7	336.85 ± 3.48	14.04 ± 0.15	9 ± 1.72	0.03552 ± 0.0085
F9	Brij 35	75:25	39.18 ± 1.99	148.27 ± 2.2	333.79 ± 5.11	13.91 ± 0.21	10 ± 2.22	0.03073 ± 0.0127
F10	SDC	95:5	64.59 ± 1.40	253.23 ± 5.1	222.62 ± 3.25	9.28 ± 0.14	32 ± 3.01	0.01183 ± 0.0083
F11	SDC	85:15	44.33 ± 1.17	144.10 ± 8.6	233.96 ± 4.74	9.75 ± 0.20	19 ± 2.95	0.02419 ± 0.0074
F12	SDC	75:25	42.49 ± 2.18	255.55 ± 2.1	210.25 ± 3.69	8.76 ± 0.15	23 ± 1.44	0.01309 ± 0.0059
TIZ solution	–	–	–	–	105.54 ± 4.13	4.39 ± 0.18	13 ± 2.56	0.00187 ± 0.0004

PC: phosphatidylcholine; EA: edge activator; SDC: sodium deoxycholate.

Q_24h: Cumulative amount of TIZ permeated per unit area; J: The flux of the drug; Kp: permeation coefficient.

Listed data are mean values ± SD (n = 3).

Figure 1. In vitro release profiles of TIZ from drug solution and transfersomal formulae: (A) F1–F6 and (B) F7–F12.

Figure 2. Transmission electron micrograph of freshly prepared transfersomal formula F5.

Figure 3. Morphology of rabbit rectal mucosa: (A) control, (B) 8 h after administration of FG and (C) 8 h after administration of TG.

Figure 4. Mean TIZ concentrations in rabbit plasma following administration of oral solution, rectal TIZ in situ gel (FG) and rectal transfersomal in situ gel (TG).

Table 2. Pharmacokinetic parameters of TIZ in rabbit plasma following administration of oral solution, FG and TG.

	Formulae
Pharmacokinetic parameters	Oral solution	FG	TG
Cmax (ng/ml)	75.04 ± 11.86	43.16 ± 9.36	144.31 ± 11.12
Tmax (h)	0.5 ± 0.00	0.75 ± 0.25	1 ± 0.00
Ke (h^−1)	0.203 ± 0.07	0.0962 ± 0.001	0.0692 ± 0.0074
t1/2 (h)	3.41 ± 0.89	7.21 ± 0.04	10.13 ± 1.08
AUC0–24 (ng h/ml)	164.13 ± 7.58	204.23 ± 20.90	314.68 ± 12.72
AUC0–∞ (ng h/ml)	173.49 ± 16.61	239.83 ± 28.11	379.48 ± 21.92
MRT (h)	4.71 ± 0.99	10.93 ± 0.53	12.03 ± 2.03
Frel (%)	100	138.24	218.73

C_max: maximum drug concentration in plasma; T_max: time to reach C_max; K_e: elimination rate constant; t_1/2: terminal half-life; AUC_0–24: area under plasma concentration–time curve from 0 to 24 h; AUC_0–∞: total area under plasma concentration–time curve; MRT: mean residence time; F_rel: relative bioavailability. Listed data are mean values ± SD (n = 3).