Data on optimization and drug release kinetics of nanostructured lipid carriers containing ondansetron hydrochloride prepared by cold high-pressure homogenization method

Nanostructured lipid carriers (NLCs), the second generation of lipid nanoparticles could enhance the drug loading capacity and minimize the drug expulsion during storage [1,2]. They are prepared from mixtures of solid and liquid lipids [3,4]. The article described the data for the preparation, optimization, and drug release studies of NLCs loaded with ondansetron hydrochloride (OSH), a water-soluble drug. The OSH-loaded NLCs were prepared using a modified cold high-pressure homogenization method. The NLCs were optimized for various parameters of formulation and preparation process on the basis of particle size (PS), polydispersity index (PI), entrapment efficiency (EE), and drug loading (DL). The dataset presented here supports “Nanostructured lipid carriers containing ondansetron hydrochloride by cold high-pressure homogenization method: Preparation, characterization, and pharmacokinetic evaluation” [5].


Data
shows the preparation process of NLCs using a modified high-pressure homogenization method. Figs. 2 and 3, Tables 1A and 1B presents validation data of the HPLC method for OSH analysis. Table 2 represents the solubility of OSH in various liquid oils, which can be used to select the proper one for NLCs preparation, since a liquid lipid with a higher drug solubility may result in a better drug loading capacity [1e7]. Various parameters of the formulation were optimized on the basis of their influences on PS, PI, EE, and DL. These parameters included pH of the aqueous phase (Table 3), solvent (Table 4A) and solid lipid (Table 4B). Table 5, Figs. 4 and 5 show PS and PI of different formulations before and after homogenization, which can be useful to evaluate the effects of homogenization on NLCs. Fig. 6 presents FTIR spectra of OSH, tristearin, Phosal® 53MCT, and F10 NLCs formulation. In vitro release data were fitted to various kinetic models. Tables 6 and 7 exhibit parameters of these kinetic models after fitting. The results can be valuable to investigate the release mechanism of drug from NLCs.

Preparation of NLCs using cold high-pressure homogenization method
NLCs were prepared using a modified cold high-pressure homogenization method (Fig. 1). Tristearin or Precirol® ATO 5 (solid lipid), Phosal® 53 MCT (liquid lipid), and the drug were dissolved in ethanol at 70±2 C to prepare the lipid phase. Tween® 80 was dissolved in deionized water or various buffer solutions (pH 2.0e12.0) to prepare the aqueous phase. The aqueous phase was maintained at 4±2 C. The lipid phase was transferred to the aqueous phase under magnetic stirring at 1,000 rpm. The mixture was continuously stirred at 4±2 C for 2 h to obtain the coarse NLCs suspension. It was then subjected to high-pressure homogenization (Emulsiflex C3, Avestin, ON, Canada) at 0-4 C. The homogenization condition (pressure and cycle number) was varied [5].

HPLC method for OSH analysis
An HPLC system (1260 Infinity, Agilent Technologies, CA, USA) consisted of a quaternary pump, an autosampler, and a UV detector. A reversed-phase column (Luna C18, 5 mm, 250 Â 4.6 mm, Phenomenex, CA, USA) was used to separate samples. The mobile phase was acetonitrile/0.02 M acetate buffer pH 4.8 (40/60, V/V). The flow rate was 1.0 mL/min. The injection volume was 10 ml, and the detection wavelength was 310 nm.

Specificity
Specificity of the HPLC method was demonstrated by comparing the chromatograms of a blank sample and a standard sample. Fig. 2 shows chromatograms of the blank sample and OSH standard solution (10 mg/mL in the mobile phase). The typical chromatogram of OSH standard solution exhibits a sharp and well-resolved peak. There is no observation of visual peak in the blank sample chromatogram. The retention time of OSH peak is approximately 4.7 min. The peak symmetry is 0.80 and peak tail factor is 1.20. The chromatogram of a sample from release study (Fig. 2C) shows OSH peak at about 4.7 min with peak symmetry of 0.81 and peak tail factor of 1.20.

System suitability
The system suitability of the developed HPLC method was demonstrated by various parameters including injection repeatability, peak tailing factor, and peak theoretical plate number. Chromatogram      Table 5 Effect of high-pressure homogenization (HPH, 500 bars Â 6 cycles) on particle size and polydispersity index of NLCs (Mean ± SD, n ¼ 3 of OSH standard solution reveals a peak with the peak tailing factor of 1.20 and peak theoretical plates (USP) of more than 8890. Six injections of a standard solution (10 mg/mL) exhibits RSD ¼ 0.4%. These results suggest that the HPLC system was suitable for OSH analysis.

Linearity
A series of three replicates of five standard solutions with concentrations of 0.5, 1, 2, 5, and 10 mg/mL were analyzed using HPLC method. The relationship between OSH concentration and peak area is shown in Table 1A

Table 6
Parameters of various kinetic models after fitting release data of different NLCs.
Zero-order First-order Higuchi Hixson-Crowell

Accuracy and precision
The percentage of variation coefficient (%CV) and percentage of recovery were calculated to demonstrate accuracy and precision, respectively. Three replicates at five different concentrations (0.5, 1, 2, 5, and 10 mg/mL) were used. The intraday accuracy and precision were analyzed within one day whereas the inter-day values were assessed over 3 different days. The results for accuracy and precision are illustrated in Table 1B. The precision of the HPLC assay ranges from 0.57 to 1.07% (intra-day) and from 0.43 to 2.84% (inter-day). The intra-day accuracy of the assay ranges from 98.06 to 101.88% and the inter-day accuracy ranges from 99.26 to 102.62%. The results reveals that the developed HPLC method is accurate and reliable for OSH determination.

OSH solubility in liquid lipids
OSH solubility in liquid lipids was determined as previously reported [6,7]. An excess amount of OSH was dispersed in a glass vial containing a liquid lipid. The vials were vortex-mixed for dispersion of the drug. They were then sealed and shaken (50 rpm, 48 h) at 37 ± 0.5 C using a shaking water bath. The samples were centrifuged at 14,000 rpm for 15 min, and the supernatants were collected and suitably diluted with ethanol. The samples were filtered using 0.45 mm membranes and analyzed by HPLC. Results of solubility studies were shown in Table 1.

Particle size analysis
PS and PI were determined by dynamic light scattering using a particle size analyzer (Zetasizer Nano-S90, Malvern Instruments, UK). After diluting 20 times with deionized water, samples were measured at 25 C with a fixed detector angle of 90 .

EE and DL determination
The EE and DL were calculated by these equations: EE (%) ¼ OSH entrapped amount/Total OSH amount x 100. DL (%) ¼ OSH entrapped amount/(OSH entrapped amount þ Lipid added amount) x 100. OSH entrapped amount was calculated by subtracting the free OSH amount from the total OSH amount in the suspension [8]. The free OSH amount was determined by ultra-filtration centrifugation (14,000 rpm, 1 h) using a centrifugal filter unit (MWCO 10,000, Amicon® Ultra, Millipore, MA, USA). The free OSH in the filtrate was diluted with the mobile phase and analyzed using the HPLC method. The total OSH amount was determined by dissolving NLCs suspension in ethanol at 60 C, diluting with the mobile phase, and quantifying by HPLC.

Fourier-transform infrared spectroscopy (FTIR)
An FTIR spectrophotometer (Tensor 27, Bruker, MA, USA) was used to analyze OSH, tristearin, Phosal® 53MCT, and the lyophilized F10 NLCs. FTIR spectra were recorded in the range of 500e4000 cm À1 with a resolution of 4 cm À1 for 16 times.

Mathematical modeling of release data
Following the in vitro drug release studies by dialysis bag method [9], data were fitted to various kinetic models (Zero-order, first-order, Higuchi, and Hixson-Crowell) using DDSolver, a recently developed program [10]. The mechanism of drug release was studied using the Korsmeyer-Peppas equation: F ¼ k.t n , (F is the fraction of drug release, k is release constant, and n is diffusional exponent). The value of n could indicate the mechanism of drug release (n 0.5: Fickian diffusion, 0.5 < n 0.9: non-Fickian transport, and n ! 0.9: case-II transport) [11].