Formulation and evaluation of niosomes-based chlorpheniramine gel for the treatment of mild to moderate skin allergy

Figures & data

Table 1. Experimental plan for niosomal dispersion formulation: (a) Three factorial design 2³, and (b) Coded level translation in actual units.

(a) Formulation Codes	Coded factor levels			Composition of factors (g) (Independent Variables)
	A	B	C	A (cholesterol)	B (Span-60)	C(Span-80)
N1	–	–	–	0.10	0.10	0.05
N2	+	–	–	0.30	0.10	0.05
N3	–	+	–	0.10	0.20	0.05
N4	+	+	–	0.30	0.20	0.05
N5	–	–	+	0.10	0.10	0.10
N6	+	–	+	0.30	0.10	0.10
N7	–	+	+	0.10	0.20	0.10
N8	+	+	+	0.30	0.20	0.10
(b) Coded levels	–	+
A(Cholesterol)	0.10	0.30
B(Span-60)	0.10	0.20
C(Span-80)	0.05	0.10

Table 2. Composition of CPM loaded niosomes displaying amount (g) of all factors used in formula to make 100 g niosomal dispersion formulation.

Ingredients	N1	N2	N3	N4	N5	N6	N7	N8
Cholesterol	0.10	0.30	0.10	0.30	0.10	0.30	0.10	0.30
Span-60	0.10	0.10	0.20	0.20	0.10	0.10	0.20	0.20
Span-80	0.05	0.05	0.05	0.05	0.10	0.10	0.10	0.10
DCM	10.0	10.0	10.0	10.0	10.0	10.0	10.0	10.0
CPM	2.0	2.0	2.0	2.0	2.0	2.0	2.0	2.0
PBS (pH 7.4)	Q.S	Q.S	Q.S	Q.S	Q.S	Q.S	Q.S	Q.S

DCM = Dicholoromethane, CPM = Chlorpheniramine maleate, PBS = Phosphate buffer saline, Q.S. =Quantity sufficient to make 100 g.

Figure 1a. (a) Optimised Niosomes (N3) 3D Surface plot of % Drug release response at y = pH 6. (b) Optimised Niosomes N3 interaction diagram.

Figure 1b. (b) Optimised Niosomes N3 interaction diagram.

Figure 2. calibration (Linear regression) Curve at 265 nm (Phosphate buffer pH 6). In the stated equation (Y = 0.0217x + 0.0414), Y is UV absorbance at 265 λ_max, m is slope (0.0217), x is concentration (µg/ml) of CPM, b is the intercept (0.0414), and R² is correlation coefficient (0.9964).

Figure 3. FTIR peaks of a = drug (CPM), b = cholesterol, c = span-60, d = span-80, e = PEG-1000, f = PG, g = carbopol-940, and h = the optimised niosomal gel of CPM (N3).

Figure 4. SEM of optimised nisomal gel of CPM (N3). Where,a = SEM of niosomal gel at 4000 magnification, b = SEM of niosomal gel at 10,000 magnification, and c&d = SEM of niosomal gel at 15,000 magnification.

Figure 5. TG/DTA of optimised niosomal Gel of CPM (N3).

Figure 6. In vitro release (%) of CPM from Niosomal gel at pH 6.

Table 3. Drug release kinetics of optimised CPM niosomal gel (N3) at pH 6.

Form.	Zero order			First order			Higuchi			Korsmeyer-Peppas				Hixon Crowell
CPM-NG*	R^2	K0	A/C	R^2	K1	A/C	R^2	KH	A/C	R^2	Kkp	n	A/C	R^2	KHC	A/C
	0.40	0.07	132.87	0.85	0.002	110.2	0.81	2.27	114.83	0.83	2.59	0.47	116.74	0.79	0.001	116.8

*CPM-NG = Niosomal Gel of CPM.

Figure 7. a = Capsicum induced allergic skin area of Rabbit and b = CPM niosomal gel treated skin area of rabbit.

Table 4. Pharmacokinetic parameters of CPM (10.00 mg) (niosomal gel) applied topically on allergenic rabbits.

Parameters	Unit	Values (mean ± SD)
Cmax	μg/ml	43.76 ± 0.200
Tmax	h	0.75 ± 0.00
t1/2	h	7.338 ± 1.92
AUC0-t	μg/ml × h	57.46 ± 0.29
AUC0-α	μg/ml × h	149.86 ± 27.43
Cl/F	(mg)/(μg/ml)/h	0.0687 ± 0.013
Vz/F	(mg)/(μg/ml)	0.75 ± 0.072

Note: C_max is Peak serum concentration, T_max is Time to reach peak serum concentration, t_1/2 is Half-life, AUC_0-t is Area under the plasma concentration time curve when time range from 0-t (where t = 4h), AUC_0-α, is Area under the plasma concentration time curve when 0-infinity, Cl/F is Clearance/bioavailability, Vz/F is Volume of distribution/Bioavailability.

Figure 8. (a) Normal rabbit skin tissue histology; (b–e) excised capsicum treated rabbit skin tissues; (f, g) 40× power, enlarged view, (h) 10× power, (i) excised CPM niosomal gel treated rabbit skin tissues stained with haematoxylin and eosin (high magnification).

Data availability statement

All the data has been incorporated into this article.