Formulation and evaluation of metformin hydrochloride-loaded niosomes as controlled release drug delivery system

Figures & data

Table 1. MH niosomal formulations expressed as molar ratios of lipid components.

	Batches
Components	Blank	MN1	MN2	MN3
Span 40	150	150	150	150
Chol	40	40	40	40
DCP	–	–	10	–
DOTAP	–	–	–	10
MH	−ve	+ve	+ve	+ve

Chol, cholesterol; DCP, dicetyl phosphate; DOTAP, 1,2-dioleoyl-3-trimethylammonium-propane, chloride salt; MH, metformin hydrochloride; +ve, presence of MH; −ve, absence of MH.

Table 2. Properties of MH-loaded niosomes.

Batch code	Mean size (nm) (Z average)	Polydispersity index	Zeta potential (mV)	Entrapment efficiency %
Blank	289.3 ± 1.9	0.515 ± 0.6	−55.6 ± 7.5	–
MN1	296.5 ± 3.4	0.75 ± 0.4	−16.6 ± 1.4	87.78
MN2	384.6 ± 2.2	0.26 ± 0.3	−26.9 ± 1.0	92.62
MN3	223.5 ± 2.7	0.38 ± 0.1	+8.7 ± 1.2	83.36

Figure 1. Effect of lipid composition on the release profile of metformin hydrochloride. The data represent the mean ± SD of six determinations.

Figure 2. Transmission electron micrograph of metformin hydrochloride-loaded niosomes (a) MN2 and (b) MN3.

Figure 3. Blood glucose concentration after oral administration of free MH solution or MH-loaded niosomes (MN3). The data represent the mean ± SEM of six determinations.

Figure 4. Serum level of metformin hydrochloride after oral administration of free MH solution or MH-loaded niosomes (MN3). The data represent the mean ± SEM of six determinations.

Table 3. Serum levels of glucose and metformin in the different studied groups after oral administration of free MH solution or MH-loaded niosomes (MN3).

		Glucose concentration (mg/dl)			Metformin concentration (µg/ml)
Groups #	Groups description	Free MH solution	MH-loaded niosomes (MN3)	p Value	Free MH solution	MH-loaded niosomes (MN3)	p Value
1	Normal control	89.58 ± 7.8	87.43 ± 6.9	0.8406	0.0	0.0	–
2	Diabetic control	208.12 ± 18.6	207.65 ± 16.8	0.9854	0.0	0.0	–
3	Diabetic + metformin (after 1 h)	155.65 ± 12.3	180.78 ± 14.5	0.3896	8.23 ± 1.7	7.27 ± 1.2	0.6544
4	Diabetic + metformin (after 2 h)	177.67 ± 14.9	160.23 ± 13.7	0.4091	7.37 ± 1.3	8.13 ± 0.98	0.6506
5	Diabetic + metformin (after 4 h)	213.32 ± 18.9	112.35 ± 10.9	0.0009	5.91 ± 0.63	8.56 ± 0.83	0.0292
6	Diabetic + metformin (after 6 h)	217.47 ± 16.7	204.12 ± 13.5	0.5481	2.56 ± 0.45	5.32 ± 0.95	0.0254
7	Diabetic + metformin (after 8 h)	220.45 ± 14.2	212.94 ± 16.1	0.7337	Not detectable	2.14 ± 0.08	<0.0001
8	Diabetic + metformin (after 24 h)	275.62 ± 21.6	280.53 ± 19.8	0.8703	Not detectable	Not detectable	–

Values are expressed as mean ± standard errors.

p Values of <0.05, <0.01 and <0.001 will be considered statistically significant, highly significant and very highly significant, respectively.

Table 4. Pharmacokinetic parameters of blood glucose levels following oral administration of free MH solution or MH-loaded niosomes (MN3).

	Parameters of activity
Formulations	AAC0–8 (mg h/dl)	Max. response (mg/dl)	Tmax (h)
Free MH solution	155.0 ± 13.6	52.47 ± 6.3	1
MH-loaded niosomes (MN3)	332.5 ± 15.7	95.3 ± 5.9	4

Values are expressed as mean ± standard error; Max. response, maximum hypoglycemic response; T_max, time of maximum hypoglycemic response; AAC_0–8, area above the blood glucose levels–time curve over 8 h.

p Values of <0.05, <0.01 and <0.001 will be considered statistically significant, highly significant and very highly significant, respectively.