Penetration enhancer-containing spanlastics (PECSs) for transdermal delivery of haloperidol: in vitro characterization, ex vivo permeation and in vivo biodistribution studies

Figures & data

Table 1. (a) Composition and in vitro characterization of F1, F2 and the prepared PECSs and (b) ex vivo permeation parameters of F1, F2 and the prepared PECSs compared to Hal solution.

	Composition			In vitro measurements^c
Formula^a	Span^® 60 (mg)	Tween^® 80 (mg)	PE^b	EE%	PS (nm)	PDI	ZP (mV)
(a)
F1	400	100	–	95.4 ± 1.7	240.9 ± 10.3	0.39 ± 0.03	−32.1 ± 1.7
F1L	400	100	Labrasol^®	60.3 ± 3.0	439.5 ± 43.8	0.51 ± 0.12	−37.9 ± 1.0
F1T	400	100	Transcutol^®	61.1 ± 3.9	563.6 ± 35.1	0.49 ± 0.17	−37.9 ± 2.1
F1G	400	100	Tetraglycol^®	93.7 ± 2.2	471.3 ± 69.8	0.57 ± 0.18	−38.6 ± 0.8
F2	300	200	–	75.3 ± 9.9	189.3 ± 3.3	0.57 ± 0.10	−30.6 ± 1.5
F2L	300	200	Labrasol^®	50.5 ± 3.5	195.7 ± 4.0	0.53 ± 0.07	−37.2 ± 1.0
F2T	300	200	Transcutol^®	47.5 ± 1.1	299.6 ± 8.3	0.76 ± 0.08	−36.8 ± 1.2
F2G	300	200	Tetraglycol^®	72.5 ± 2.5	363.2 ± 20.7	0.57 ± 0.01	−30.6 ± 2.2
		(Q) (μg/cm^2)^c			(J) (µg/cm^2/h)^c
Formula^a		Q24	Q36	Q48	J24	J36	J48
(b)
F1		32.2 ± 9.6	78.2 ± 7.8	184.5 ± 42.7	1.5 ± 0.5	2.2 ± 0.4	3.6 ± 0.8
F1L		93.1 ± 14.8	148.1 ± 3.56	208.8 ± 4.5	4.4 ± 0.7	4.5 ± 0.0	4.6 ± 0.00
F1T		73.9 ± 6.9	120.5 ± 11.8	201.3 ± 13.3	3.5 ± 0.3	3.6 ± 0.3	4.2 ± 0.1
F1G		56.1 ± 13.9	107.3 ± 17.4	204.5 ± 20.8	3.5 ± 1.2	3.6 ± 0.6	4.2 ± 0.0
F2		60.6 ± 13.6	102.9 ± 9.0	158.1 ± 11.6	2.8 ± 0.6	3.1 ± 0.2	3.5 ± 0.2
F2L		86.3 ± 0.3	110.9 ± 23.2	236.4 ± 100.4	3.9 ± 0.1	3.4 ± 0.4	4.7 ± 1.6
F2T		72.6 ± 13.5	93.7 ± 20.8	209.8 ± 90.2	3.4 ± 0.6	3.0 ± 0.6	4.2 ± 1.6
F2G		59.1 ± 0.7	86.1 ± 1.6	147.7 ± 3.0	2.8 ± 0.0	2.7 ± 0.0	3.1 ± 0.1
Hal solution		2.7 ± 2.4	6.1 ± 0.5	16.6 ± 6.3	0.1 ± 0.1	0.2 ± 0.0	0.3 ± 0.0

PECSs: Penetration enhancer-containing spanlastics; PE: penetration enhancer; EE%: percentage entrapment efficiency; PS: particle size; PDI: polydispersity index; ZP: zeta potential.

^a All formulae contained 2.5 mg Hal/ ml and total volume was 10 ml.

^b PE concentration was 1 % w/v.

^c All values are reported as mean ± SD (n = 3).

Figure 1. (a) and (b): Permeation plots of Hal from different spanlastics and penetration enhancer containing spanlastics compared to drug solution and (c)Transmission electron microscope image of selected formula.

Figure 2. (a) Release profiles of Hal from SF, SF-hydrogel and Hal solution, (b) SF-hydrogel rheological characterization and (c) Effect of storage on Hal release of from SF-hydrogel.

Figure 3. Effect of different variables (a) amount of dil-SF, (b) amount of reducing agent (NaBH4), (c) pH and (d) reaction time – on percent radioactive yield of ^99mTc-SF.

Figure 4. Percentage radioactivity (%R/g) in different body organs and blood at different time points after transdermal application of ^99mTc-SF-hydrogel or oral administration of ^99mTc-SF.

Figure 5. Brain/blood ratio of radioactive complex after transdermal application of ^99mTc-SF-hydrogel or oral administration of ^99mTc-SF.