Development and characterization of nanoemulsion as carrier for the enhancement of bioavailability of artemether

Figures & data

Figure 1. Schematic representation of nanoemulsion.

Table I. Selection of optimized concentration of oil.

Formulation code	Oil	Surfactant 1	Surfactant 2	Inference
C1	Coconut oil	Soya lecithin	Tween 80	Emulsion formed
C2	Coconut oil	GMS	Soya lecithin	Separation
C3	Coconut oil	GMS	Tween 80	Separation
C4	Coconut oil	Soya lecithin	Pluronic F68	Emulsion formed
C5	Coconut oil	GMS	Pluronic F68	Emulsion formed
C6	Coconut oil	Span 80	Tween 80	Stable emulsion formed
S1	Soyabean oil	Soya lecithin	Tween 80	Separation
S2	Soyabean oil	GMS	Soya lecithin	Precipitation
S3	Soyabean oil	GMS	Tween 80	Emulsion formed
S4	Soyabean oil	Soya lecithin	Pluronic 68	Precipitation
S5	Soyabean oil	GMS	Pluronic 68	Separation
S6	Soyabean oil	Span 80	Tween 80	Emulsion formed

GMS, Glyceryl monostearate.

Table II. Selection of optimized concentration of surfactant (n = 3).

Formulation code	Oil	Surfactant 1	Surfactant 2	Size (nm)	PDI
F1	Coconut oil	Glyceryl monostearate	Tween 80	354.4 ± 5.8	0.337 ± 0.02
F2	Coconut oil	Soya lecithin	Tween 80	337 ± 8.9	0.407 ± 0.06
F3	Coconut oil	GMS	Soya lecithin	244.8 ± 6.6	0.405 ± 0.05
F4	Coconut oil	GMS	Pluronic 68	460.5 ± 8.8	0.381 ± 0.02
F5	Coconut oil	Pluronic 68	Soya lecithin	368.5 ± 6.0	0.327 ± 0.04
F6	Coconut oil	Span 80	Tween 80	192.8 ± 5.3	0.287 ± 0.02
F7	Coconut oil	Span 60	Tween 80	267.8 ± 9.8	0.398 ± 0.02
F8	Coconut oil	Span 20	Tween 80	287.4 ± 10.7	0.333 ± 0.03

Mean ± Standard deviation (SD), n = 3.

Table III. Optimization of sonication time.

Formulation code	Oil:surfactant ratio (%)	Water (%)	Sonication time (min)	Particle size (nm)	PDI
T1	Oil:Span 80: Tween 80 (5:0.5:5)	82.5	1	206.5 ± 7.0	0.397 ± 0.02
T2			1.5	191.7 ± 5.5	0.253 ± 0.03
T3			2	174.6 ± 4.3	0.203 ± 0.03
T4			2.5	229.3 ± 4.8	0.342 ± 0.02
T5			3	249.5 ± 2.8	0.336 ± 0.04
T6			3.5	263.8 ± 4.5	0.218 ± 0.02
T7			4	275.9 ± 15.4	0.365 ± 0.03

Table IV. Optimized composition for final formulation.

S. No.	Composition	Quantity (% v/v)
1	Coconut oil	5
2	Span 80	0.5
3	Tween 80	5
4	Ethanol	5

Figure 2. TEM images of optimized artemether nanoemulsion.

Table V. Optimized formulation along with their parameters (± S.D., n = 3).

S. No.	Parameters	Values
1.	Particle size (PS)	79.0 ± 5.7 nm
2.	Polydispersibility index (PDI)	0.220 ± 0.05
3.	Zeta potential (ZP)	−15.54 ± 0.21 mV
4.	Percentage drug release (% DR)	91.5 ± 2.4
5.	Mean percentage transmittance (PT)	98.20 ± 0.7
6.	Refractive index (RI)	1.320 ± 0.05
7.	Viscosity (V)	17 ± 1.8 cp
8.	Sonication time	2 min
9.	Drug concentration	4 mg/ml

Table VI. Stability studies of artemether nanoemulsion under accelerated stability conditions.

Days*	0	30	60	90
Size (nm)	79.0 ± 5.7	82.19 ± 4.1	86.75 ± 4.0	88.9 ± 4.7
% Drug content	98.42 ± 0.87	97.84 ± 0.77	97.31 ± 0.76	96.98 ± 0.97
PDI	0.220 ± 0.05	0.241 ± 0.08	0.253 ± 0.07	0.259 ± 0.04
Drug release (%)	91.6 ± 0.9	‐	‐	‐

*Number of days sample was kept under accelerated stability conditions.

Figure 3. In-vitro release profile of nanoemulsion and plain drug (artemether) through dialysis bag.

Figure 4. Ex-vivo release profile of nanoemulsion and plain drug (artemether) through Intestinal Sac.

Figure 5. Drug release kinetics of optimized artemether nanoemulsion.

Figure 6. Korsmeyer–Peppas Model, where Log% CR represents Log percentage cumulative release.

Figure 7. Plasma drug concentration versus Time profile of plain drug i.e., artemether and optimized nanoemulsion formulation in Wistar rats after oral administration (dose 4 mg/kg).

Table VII. Pharmacokinetic parameters of artemether nanoemulsions as well as for plain drug after oral administration*(n = 6).

Parameters	Units	Oral artemether nanoemulsion (4 mg/kg)*	Plain drug (4 mg/kg)*
T1/2	Minutes	238.7	257.557
T max	Minutes	120	60
C max	μg/ml	0.986	0.46
AUC0–24	μg/ml/minute	308.707	113.384
AUC0–α	μg/ml/minute	430.959	167.635
MRT	minutes	394.499	410.593

AUC, Area under curve; C_max, Maximum concentration of drug; MRT, Mean residence time; T_max, Peak time when drug achieves C_max.