Carvedilol nano lipid carriers: formulation, characterization and in-vivo evaluation

Figures & data

Table 1. Composition of different Carvedilol-loaded NLC formulation.

Formulation	Stearic acid:oleic acid	Tween 80 (%, v/v)	PEG 4000 (%)	Water
F1	60:40	4.5	10	50
F2	65:35	4.5	10	50
F3	70:30	4.5	10	50
F4	55:45	4.5	10	50
F5	50:50	4.5	10	50
F6	45:55	4.5	10	50

Figure 1. Solubility of CAR in various solid and liquid lipids.

Table 2. Physicochemical evaluation parameters of Carvedilol NLC formulations.

Formulation	Size (nm)	EE (%)	PDI	DL (%)	DR (%)	DP (μg/ml)
F1	172.67 ± 2.11	81.34 ± 3.11	0.455	11.23 ± 1.12	64.96 ± 4.11	856.98 ± 31.67
F2	171.76 ± 3.76	88.56 ± 2.76	0.407	10.65 ± 0.96	71.56 ± 5.67	911.35 ± 55.42
F3	165.11 ± 5.38	83.56 ± 1.98	0.476	11.96 ± 0.76	77.55 ± 4.28	934.38 ± 41.67
F4	194.45 ± 4.71	71.39 ± 4.02	0.489	12.56 ± 0.56	78.34 ± 3.67	898.29 ± 55.53
F5	204.45 ± 3.23	76.44 ± 2.27	0.511	9.58 ± 1.21	69.25 ± 5.34	847.42 ± 64.46
F6	197.45 ± 5.12	69.45 ± 3.94	0.481	10.32 ± 1.08	63.23 ± 4.29	859.24 ± 41.43

Data presented as mean ± standard deviation.

EE, encapsulation efficiency; PDI, polydispersity index; DL, drug loading; DR, drug release; DP, drug permeate.

Figure 2. In vitro release profile of CAR-NLC versus CAR-S. Each value represents the mean ± SD (n = 3).

Table 3. In vitro release model fitting in terms of linear regression coefficient.

			Plot
S. No.	Model	Equation	X axis	Y axis	R^2 value
1	Zero order	M0–M = kt	Fraction of drug released	Time	0.887
2	First order	ln m = kt	Log % drug remaining	Time	0.943
3	Higuchi model	M0–M = kt1/2	Fraction of drug released	√ time	0.913
4	Korsmeyer–Peppas	log (M0–M) = log k + n log t	Log fraction of drug released	Log time	0.943

M₀ is initial drug content at time to and m is drug content at time t.

Figure 3. Surface morphology of CAR-NLCopt using TEM.

Figure 4. DSC image of CAR-NLC and its ingredients. (A) CAR, (B) CAR-NLC, (C) stearic acid.

Figure 5. Powder X-ray diffraction image of CAR-NLC and its ingredients. (A) Carvedilol, (B) stearic acid, (C) placebo NLC, (D) lyophilized CAR-NLC.

Figure 6. Comparative plasma concentration versus time curve of CAR-NLCopt and CAR-S after oral administration in rats. Each value represents the mean ± SD.

Table 4. In vivo absorption profile of CAR-NLCopt and CAR-S to rats after oral administration (5 mg/kg).

Parameters	CAR-NLCopt	CAR-S
Cmax (ng/ml)	1068.09 ± 36.94	304.65 ± 43.89
Tmax (h)	1.5 ± 0.16	3 ± 0.13
t1/2 (h)	6.747	4.399
AUC0−t (ngh/ml)	8881.028 ± 387.51	2243.74 ± 274.11
AUC0−∞ (ngh/ml)	9067.32 ± 223.48	4172.36 ± 115.32
AUMC0−t (ngh^2/ml)	68 572.93 ± 134.18	30 541.52 ± 110.08
AUMC0−∞ (ngh^2/ml)	77 147.93 ± 227.56	31 837.96 ± 145.85
MRT (h)	8.5 ± 1.02	6.038 ± 0.96
Kel (h^−1)	0.1023	0.1076

Table 5. Comparative antihypertensive effect of CAR-NLCopt and CAR-S on mean BP in MPA-induced hypertensive rats.

Groups	0 (h)	1 (h)	2 (h)	4 (h)	8 (h)	12 (h)	24 (h)	48 (h)	% Reduction
1	112.23 ± 9.57	119.22 ± 7.98	109.35 ± 11.38	127.44 ± 13.23	129.3 ± 7.51	111.55 ± 9.56	115.11 ± 11.55	124.78 ± 9.67	–
2	168.44 ± 7.23	176.34 ± 9.34	171.22 ± 11.34	169.44 ± 7.54	175.33 ± 8.45	169.42 ± 6.78	167.35 ± 7.22	168.45 ± 8.65	–
3	171.51 ± 9.56	141.56 ± 8.47	127.45 ± 8.11	123.55 ± 9.22	134.56 ± 12.45	146.55 ± 10.69	15.34 ± 11.51	161.43 ± 8.21	4.16
4	167.64 ± 6.24	141.31 ± 8.67	126.71 ± 8.43	117.34 ± 9.28	107.21 ± 9.45	115.55 ± 8.11	122.55 ± 11.56	138.41 ± 10.32	17.85

Group 1, normal control; Group 2, hypertensive control; Group 3, CAR-S; Group 4, CAR-NLCopt.