Preparation and characterization of nimodipine-loaded nanostructured lipid systems for enhanced solubility and bioavailability

Figures & data

Figure 1 The flowchart of the preparation process of NMP-NLC.

Abbreviation: NMP-NLC, nimodipine-loaded nanostructured lipid carrier.

Table 1 Influence of different solid lipids on particle size, PDI, zeta potential, and EE%

Solid lipid	Size (nm)	Polydispersity	Zeta potential (mV)	EE%
ATO5	76.1±0.2	0.178±0.007	−23.8±0.8	87.5±2.4
GMS	124.5±0.7	0.277±0.103	−14.5±0.2	70.6±3.6

Note: All the results are represented as mean ± SD (n=3).

Abbreviations: ATO5, Precirol ATO 5; EE%, entrapment efficiency; GMS, glyceryl monostearate; PDI, polydispersity index.

Table 2 Apparent solubility of NMP in various liquid lipids

Liquid lipid	Solubility (mg/g)
OA	4.65±0.8
IPM	12.34±1.4
EO	13.58±1.2
MCT	18.74±1.6
Labrafac PG	24.88±2.1

Note: All the results are represented as mean ± SD (n=3).

Abbreviations: EO, ethyl oleate; IPM, isopropyl myristate; MCT, medium chain triglycerides; NMP, nimodipine; OA, oleic acid; PG, propylene glycol dicaprate.

Figure 2 Formulation screening of nanostructured lipid carriers.

Notes: (A) Different ratios of solid lipid and liquid lipid (g/g) on the particle size and EE%. (B) Various ratios of drug and lipid (g/g) on the particle size and EE%. (C) Different surfactants on the particle size and EE%. (D) Different Tween 80 content (g) on particle size and EE%. Results are represented as mean ± SD (n=3).

Abbreviations: EE%, entrapment efficiency; HS 15, polyoxyethylene esters of 12-hydroxystearic acid; RH 40, hydrogenated polyoxyethylene castor oil; TPGS, vitamin E polyethylene glycol succinate.

Figure 3 Technology screening of nanostructured lipid carriers.

Notes: (A) Different shear rates (×10³ rpm) on the particle size and PDI. (B) Different homogenization pressures (MPa) on the particle size and PDI. (C) Different homogenization cycles on the particle size. Results were expressed as mean ± SD (n=3).

Abbreviation: PDI, polydispersity index.

Figure 4 Pharmaceutical characteristics of NMP-NLC in vitro.

Notes: (A) Particle size and PDI of NMP-NLC analyzed by DLS. (B) TEM morphology of NMP-NLC. Bar =50 nm. (C) In vitro drug release profile of NMP-NLC and NMP suspension in pH 1.2 simulated succus gastricus. (D) In vitro drug release profile of NMP-NLC and NMP suspension in pH 6.8 simulated intestinal fluid. (E) Particle size and PDI of NMP-NLC during 2 weeks of storage at 4°C and (F) particle size and PDI of NMP-NLC during 2 weeks of storage at 25°C. Results are expressed as the mean ± SD (n=3).

Abbreviations: NMP-NLC, nimodipine-loaded nanostructured lipid carriers; PDI, polydispersity index.

Figure 5 The crystal form of NMP-NLC.

Notes: (A) DSC thermograms of NMP coarse powder, physical mixture of lipids, and NMP and lyophilized NMP-NLC powder. (B) X-ray diffraction patterns of NMP coarse powder, physical mixture of lipids, and NMP and lyophilized NMP-NLC powder.

Abbreviations: DSC, dynamic light scattering; NMP-NLC, nimodipine-loaded nanostructured lipid carriers.

Figure 6 The FT-IR spectroscopy analysis of NMP coarse powder, physical mixture of lipids and NMP and lyophilized NMP-NLC powder.

Abbreviations: FT-IR, Fourier transform infrared spectroscopy; NMP-NLC, nimodipine-loaded nanostructured lipid carriers.

Table 3 Absorption parameters of NMP solution and NMP-NLC in different intestinal segments

Samples	Parameters	Small intestine	Colon
NMP solution	Ka (×10^−3 min^−1 )	2.99±0.08	1.00±0.16
	Papp (×10^−4 cm⋅min^−1)	5.57±0.36	1.91±0.22
NMP-NLC	Ka (×10^−3 min^−1 )	5.98±0.20*	1.79±0.03*
	Papp (×10^−4 cm⋅min^−1)	11.3±0.24*	3.94±0.35*

Notes: NMP concentration in each formulation was 30 µg/mL. Results are represented as mean ± SD (n=3).

* P<0.05, compared to the corresponding parameters of NMP solution.

Abbreviations: K_a, the absorption rate constant; NMP-NLC, nimodipine-loaded nanostructured lipid carriers; P_app, the effective permeability coefficient constant.

Figure 7 The in situ absorption of NMP-NLC in rat intestinal segments compared with NMP solution.

Notes: (A) The absorption rate (K_a) and (B) the effective permeability coefficient (P_app). Results were represented as mean ± SD (n=3). *P<0.05, compared to the corresponding parameters of NMP solution.

Abbreviation: NMP-NLC, nimodipine-loaded nanostructured lipid carriers.

Table 4 Pharmacokinetics parameters

Parameters	NMP suspension	NMP-NLC
Cmax (µg/mL)	11.887±2.464	32.516±7.151*
Tmax (h)	3.000±0.540	0.250±0.500**
t1/2 (h)	4.905±1.013	10.160±4.566
AUC0–∞ (µg/mL*h)	45.691±7.667	73.546±8.933*
AUMC0–∞ (µg/mL*h^Citation2)	382.679±3.482	818.153±2.504***
Cl/F (mg/kg)/(µg/mL)/h	0.875±0.007	0.544±0.002***
MRT (h)	8.375±0.006	11.124±0.444**

Notes: Rats were given a single oral administration at a dose of 40 mg/kg of NMP-NLC and NMP suspension. Results are represented as mean ± SD (n=7).

* P<0.05,

** P<0.01,

*** P<0.001, compared to the corresponding parameters of NMP suspension.

Abbreviations: AUC_0–∞, the area under the concentration–time curve; AUMC, the area under moment curve; Cl/F, the clearance rate in plasma; C_max, the maximum concentration; MRT, mean residence time; NMP-NLC, nimodipine-loaded nanostructured lipid carriers; T_max, the time of maximum concentration; t_1/2, the half-life of plasma.

Figure 8 Plasma concentration–time curves of the pharmacokinetic experiment.

Notes: Rats were given a single oral administration at a dose of 40000 µg/kg of NMP-NLC and NMP suspension. Results are expressed as the mean ± SD (n=7).

Abbreviation: NMP-NLC, nimodipine-loaded nanostructured lipid carriers.

FuQSunJAiXNimodipine nanocrystals for oral bioavailability improvement: role of mesenteric lymph transport in the oral absorptionInt J Pharm2013448129029723384726

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