Development of a new nanovesicle formulation as transdermal carrier: Formulation, physicochemical characterization, permeation studies and anti-inflammatory activity

Figures & data

Table I. Composition for ICV formulations (drug lipid ratio = 1:3).

S. No.	Formulation code	Composition	Molar ratio (% w/w)
1.	ICV-1	Cer 2/Chol/CS/PA	4/2.5/1/1 = 8.5
2.	ICV-2	Cer 2/Chol/CS/PA	4/2.5/1/2 = 9.5
3.	ICV-3	Cer 2/Chol/CS/PA	4/2.5/1/3 = 10.5

ICV, Ibuprofen ceramide nano vesicle; Chol, cholesterol; Cer 2, ceramide 2, PA, palmitic acid; CS, cholesteryl sulfate.

Figure 1. Micrographic images of ICV-1(× 10⁴).

Table II. Physicochemical characterization.

Formulation code	Size* (nm)	PDI*	ζ potential* (mV)	Entrapment efficiency*(%)	Viscosity† (Cps)
ICV-1	119 ± 3.08	0.144 ± 0.001	− 33 ± 1.27	78.26 ± 2.45	14743 ± 8.3
ICV-2	128 ± 3.17	0.174 ± 0.003	− 38 ± 2.36	81.74 ± 3.89	15982 ± 9.6
ICV-3	139 ± 4.15	0.191 ± 0.004	− 40 ± 2.98	87.71 ± 3.9	17014 ± 6.8

All data are expressed as mean ± S.D.; n = 3; P ≤ 0.05.

*Determinations performed on nanovesicles (ICV).

†Viscosity determined on corresponding carbopol gels.

Figure 2. In vitro release profile for nanovesicles and CG formulations in 24 h.

Table III. Physicochemical characterization and drug release of ICV-1 after 90 days at accelerated conditions.

Parameters	Temperatures/Relative humidity
	4 ± 0.5°C	25 ± 0.5°C/60% RH	40 ± 0.5°C/75% RH
Vesicles size (nm)
Initial	119 ± 3.08	119 ± 3.08	119 ± 3.08
1 month	119.5 ± 2.76	120.9 ± 3.9	121.8 ± 1.26
2 month	120.8 ± 4.34	121.5 ± 4.17	125.6 ± 3.92
3 month	121.6 ± 3.42	123.6 ± 2.65	129.8 ± 3.38
Polydispersibility index (PDI)
Initial	0.144 ± 0.001	0.144 ± 0.001	0.144 ± 0.001
1 month	0.149 ± 0.001	0.151 ± 0.002	0.158 ± 0.006
2 month	0.152 ± 0.002	0.156 ± 0.002	0.167 ± 0.002
3 month	0.154 ± 0.003	0.161 ± 0.004	0.172 ± 0.007
ζ potential (mV)
Initial	− 33 ± 1.27	33 ± 1.27	− 33 ± 1.27
1 month	− 33 ± 1.9	− 32 ± 2.7	− 32 ± 2.18
2 month	− 32 ± 2.8	− 31 ± 2.2	− 30 ± 2.1
3 month	− 31 ± 2.9	− 29 ± 2.9	− 29 ± 2.9
Entrapment efficiency (%)
Initial	78.26 ± 2.45	78.26 ± 2.45	78.26 ± 2.45
1 month	78.9 ± 2.1	78.95 ± 2.4	79.02 ± 2.3
2 month	79.28 ± 2.8	79.99 ± 1.9	80.14 ± 2.9
3 month	79.91 ± 2.3	80.25 ± 2.7	81.28 ± 1.9
% Cumulative in vitro drug release (in 24 h)
Initial	97.24 ± 1.22	97.24 ± 1.22	97.24 ± 1.22
1 month	97.99 ± 2.43	98.64 ± 2.63	98.84 ± 2.59
2 month	98.13 ± 2.46	99.07 ± 1.94	99.98 ± 3.65
3 month	98.63 ± 1.95	99.98 ± 4.09	99.43 ± 4.17 (in 22 h)

All data are expressed as mean ± S.D.; n = 3; P ≤ 0.05.

Figure 3. Permeation profile for vesicle formulations through human skin.

Figure 4. Drug content accumulated in different skin strata. SC, stratum corneum; VED, viable epidermis; D, Dermis; RF, receptor fluid.

Table IV. Permeation parameters for CG and ICVG formulations.

Formulation code	Flux (μg/cm^2/hr)	Lag time (Hrs.)	Permeation coefficient (cm/hr) × 10 ^− 5	Distribution coefficient (cm^2/hr × 10^− 3)	Enhancement ratio
CG	0.0213	2.8	0.0426	0.00125	1
ICVG-1	1.3469	0.7	2.6938	0.005	63.23
ICVG-2	0.963	1.5	1.926	0.00233	45.21
ICVG-3	0.7372	1.925	1.4744	0.001818	34.61

CG, Carbopol gel containing Ibuprofen.

Figure 5. Plasma concentration time profile for CG and ICVG-1.

Table V. Pharmacokinetic data of the CG and ICVG-1.

Formulation code	Cmax (μg/ml)	Tmax (h)	AUC (μg.hr/ml)
CG*	0.7 ± 0.031	4	7.475
ICVG-1^†	9.6 ± 0.36	8	149.1

All data are expressed as mean ± S.D.; n = 6; P ≤ 0.05.

*1 g formulation equivalent to 50 mg Ibuprofen.

†500 mg formulation equivalent to 25 mg of Ibuprofen.

Figure 6. Anti-inflammatory activity.