Thermogravimetry

The characteristics—such as particle size, form, and number, crystalline structure, melting point, zeta potential, solubility, and dispersibility—were analyzed following our previous study [21 (link),22 (link),23 (link),26 (link)]. A laser diffraction particle size analyzer, SALD-7100 (Shimadzu Corp., Kyoto, Japan), and the Dynamic Light Scattering NANOSIGHT LM10 (QuantumDesign Japan, Tokyo, Japan) were used to determine the particle size distribution. The particle form was observed by SPM-9700 (Shimadzu Corp., Kyoto, Japan), and the provided phase and height images of irbesartan were combined and expressed as atomic force microscopic (AFM) images. Moreover, the particle number was measured by NANOSIGHT LM10. The crystalline form of the lyophilized IRB-P and IRB-NC suspensions was analyzed by a powder X-ray diffraction (XRD) method using Mini Flex II (Rigaku Co., Tokyo, Japan), and the melting point was evaluated by thermogravimetry–differential thermal analysis (TG-DTA) measurements under a nitrogen atmosphere using the simultaneous TG-DTA apparatus DTG-60H (Shimadzu Corp., Kyoto, Japan). The zeta potential was measured by a micro-electrophoresis zeta potential analyzer, model 502 (Nihon Rufuto Co., Ltd., Tokyo, Japan). In addition, the solubility of irbesartan in the IRB-NC suspensions was measured as follows: the IRB-NC suspensions were centrifuged at 100,000× g using a Beckman Optima^TM MAX-XP Ultracentrifuge (Beckman coulter, Osaka, Japan) to separate into soluble and nonsolubilized irbesartan. After this, the concentration of soluble irbesartan was measured by the HPLC method described above. In this study, the concentration of soluble irbesartan is expressed as the solubility of irbesartan. Then, 3 mL of the IRB-NC suspensions in a 5 mL test tube were incubated in the dark at 22 °C for one month (30 days) to evaluate the dispersibility, which was determined by measurement of the irbesartan concentration in the sample collected from the upper 90% of the test tube over time.

The starting material was a diatomite, i.e. a tripolaceous siliceous rock (Tripoli rock) cropping out in the Crotone Basin in southern Italy. Tripoli was analysed by X-ray diffraction (XRPD) with a Siemens D5000 operating with a Bragg-Brentano geometry; CuKα = 1.518 Å, 40 kV, 40 mA, 2–35° scanning interval, step size 0.020° 2θ with a scan rate of 13 sec/step. Characterization of this material revealed a mineralogical assemblage mainly consisting of an amorphous siliceous fraction (diatoms and sponges, visible as the bulge in the range 17–25°2theta) with minor presences of quartz, montmorillonite, chlorite, kaolinite, K-micas and small amounts of calcite (Fig. 1). Chemical analysis of Tripoli rock is reported in Table 1 and was performed by X-ray fluorescence analysis (Axios-Max Advanced Panalytical; 60KV; 160 mA; 4000 W; 0.0001°2 θ). We considered the value of LOI of 1 g of sample obtained in ceramic meltpots running in an oxidizing furnace.Figure 1

XRPD pattern of “Tripoli rock”.

Table 1

Chemical composition of “Tripoli rock” analysed by X-ray fluorescence.

	Tripoli rock
SiO2	81.07 (0.45)
TiO2	0.26 (0.02)
Al2O3	5.03 (0.02)
Fe2O3	2.14 (0.03)
MnO	0.07 (0.01)
MgO	1.11 (0.01)
CaO	1.72 (0.03)
Na2O	0.25 (0.02)
K2O	0.68 (0.02)
P2O5	0.07 (0.01)
LOI	7.73 (0.03)
Tot.	100.13 (0.18)

The standard deviation values calculated for three analyses are reported in brackets. LOI: loss on ignition.

The synthesis of leucite was conducted through the mixing of silicate and aluminate solutions. These solutions were prepared according to the procedure already described in Novembre et al.^{24 (link)} In the present study, 5.19 g of the ground and powdered Tripoli material were treated with HNO₃ (65%), in order to dissolve the calcite fraction in order to remove the soluble calcite fraction from the starting material. The diatomitic sample (ca. 5 g after the HNO₃ treatment) was added to 50 mL of KOH (6.8%). This solution was thoroughly mixed with a magnetic stirrer for 2 h and then put in a teflon reactor/bomb and heated in an oven at 80 °C for 24 h. After filtration, the remnant solid and insoluble fraction, which consisted of clay minerals and quartz, was separated from the silicate solution. The resulting molar composition of the solution was 0.060 K₂O–0.026SiO₂–0.625H₂O with traces as follows: 2.01 ppm Mg, 2.11 ppm Ca and Al, Ti and Mn lower than 0.1 ppm. Based on a mass balance calculation following this step-wise chemical separation process, the Tripoli rock was determined to be composed of: 63.27 wt% amorphous silica (diatoms and sponges), 32 wt% of clay minerals and quartz, and 3.83 wt% calcite.
The aluminate solution was prepared as follows: 0.45 g of Al(OH)₃ (65%) was mixed with 50 mL of KOH (6.8%). The obtained aluminous solution with a composition of 0.060 K₂O–0.0076Al₂O₃–0.625 H₂O (Mn, Ti and Mg < 0.01 ppm; Fe < 0.4 ppm; K, Ca and Si < 0.2 ppm) was then heated at 100 °C for one hour.
A series of three syntheses were carried out by varying the volume ratio of the two solutions according to Table 2.Table 2

Starting mixture and relative obtained mineralogical assemblages of experimental runs.

synthesis run	starting mixture	SiO2/Al2O3	mineralogical assemblage
1	10 ml siliceous sol + 10 ml aluminous sol	3.40	KAlSi2O6 + KAlSIO4-O1 (1.5–20 h); KAlSi2O6 (24 h)
2	12.5 ml siliceous sol + 7.5 ml aluminous sol	5.70	KAlSi2O6 + KAlSIO4-O1 (1.5–15 h); KAlSi2O6 (20 h)
3	10 ml siliceous sol + 5 ml aluminous sol	6.80	KAlSi2O6 + KAlSIO4-O1 (3 h); KAlSi2O6 (15–20 h)

The reactants were vigorously mixed for two hours with a magnetic stirrer. Each mixture was heated inside an autoclave at 150 °C and ambient pressure for a duration of one hour. The hydrothermally derived gel precursors were recovered from the reactors, filtered from the solution, thoroughly washed with distilled water and dried in an oven at 40 °C for 24 hours. These gel products were examined by XRPD analysis (Fig. 2) in order to assess their amorphous character. The three gel precursors were then calcined at 1000 °C with periodic sampling carried out at scheduled intervals.Figure 2

XRPD patterns of the hydrothermal gel precursors. (a): synthesis run 1; (b): synthesis run 2; (c) synthesis run 3.

All intermediate and final products of the three syntheses were analysed by XRPD under the same operating conditions as those for the “Tripoli rock” analysis. Identification of phases and relative peak assignment were made with reference to the following JCPDS codes: 00-038-1423 for leucite and 00-011-0579 for KAlSIO₄-O1. The amounts of both the crystalline and amorphous phases in the synthesis powders were estimated using Quantitative Phase Analysis (QPA) applying the combined Rietveld and Reference Intensity Ratio (RIR) methods; corundum NIST 676a was added to each sample, amounting to 10%, and the powder mixtures were homogenized by hand-grinding in an agate mortar. Data for the QPA refinement were collected in the angular range 5–70° 2θ with steps of 0.02° 2θ and 10 s step⁻¹, a divergence slit of 0.5° and a receiving slit of 0.1 mm.
Data were processed with the GSAS software²⁸ and the graphical interface EXPGUI^{29 (link)}. The unit cell parameters were determined, starting with the structural models proposed by Dove et al.³⁰ for leucite and Kremenovic et al.^{31 (link)} for KAlSiO₄-O1. Parameters were refined following Novembre et al.^{25 (link)}.
Analysis of synthesized powders was performed by inductively coupled plasma optical emission spectroscopy (ICP-OES, Perkin Elmer Optima 3200 RL) after alkaline fusion of the sample in a Pt crucible (lithium meta-tetra borate pearls, at 3/2 ratio) and subsequent acid solubilization^{27 (link)}.
Scanning electron microscope (SEM) analyses were carried out with a JEOL JSM-840 with operating conditions of 15 kV and window conditions ranging from 18 to 22 mm, following the procedure as explained in Ruggieri et al.^{32 (link)}.
Vibrational spectra of the synthesized products were obtained with an Infrared spectrometer FTLA2000, equipped with SiC (Globar) filament source, KBr beamsplitter and DTGS detector. Samples were prepared according to the method of Robert et al.^{33 (link)} using powder pressed pellets (sample/KBr ratio of 1:100); spectra were processed with the program GRAMS-Al.
Thermal behaviour of gel precursors were studied by differential thermal analysis and thermogravimetry (DTA-TG) by means of a Mettler TGA/SDTA851^e instrument (10°/minute from 30° to 1100 °C, using an approximate sample weight of 10 mg in Al₂O₃ crucible).
Density of leucite was measured by He-picnometry using an AccuPyc 1330 pycnometer.

The Ag NPs were characterized by spectra obtained by UV-vis spectrophotometer (Shimadzu) at 380 to 500 nm. Fourier transform infrared (FT-IR) spectra (Bruker, UK) were obtained in the range of 400 to 4000 cm⁻¹ by KBr pellet method to determine the functional groups. The metallic Ag NPs were examined using an x-ray diffractometer (PANlytical Xpert Pro) equipped with a CuKá radiation source at a generator setting of 40 kV/30 mA and data was collected in the range of 9.971°–99.955°. For SEM-EDAX, a small quantity of the powder was spread over the carbon tape and inserted into the chamber. A series of images were taken (System Quanta Inspect F) at different voltages and magnifications, to understand the morphology and chemical composition of the sample. Transmission electron microscopic examination of the particles was undertaken to determine the size distribution of Ag NPs. JEOL_JEM-2010 instrument was used to obtain the high resolution transmission electron microscopy (HRTEM) images of the samples and the selected area electron diffraction (SAED). For these experiments, the samples were subjected to ultra-sonication in ethanol medium to disperse the fine powder onto the copper grids. These TEM images were used to investigate the morphology while the SAED confirmed the nature of crystallinity. XPS experiments were carried out on the Krotas Axis Ultra^DLD Model at the base pressure of 1 × 10⁻⁹ Torr and the working pressure at 5 × 10⁻⁹ Torr, with Mono Al Kα as irradiation source of energy (1486.71 eV operated at 15 KV and 5 mA) to determine the chemical composition and the valence states of the prepared material. Thermo-gravimetric-differential scanning calorimetry (TGA-DSC) analysis with 50 mg of the powder in a small alumina crucible (Universal V4.5 A TA instruments of model SDT 2600 V20.9 Build 20) was carried out using N₂ gas with a ramp (heating) of 20 °C/min.

After BSTS crystal growth, the ampoule was gently broken and the material was cleaved via razor blade and exfoliated to produce a thin layer for elemental composition detection using energy-dispersive X-ray spectroscopy (EDS, HITACHI S-4800 High Resolution Field Emission Scanning Electron Microscopy (SEM)) operating at an acceleration voltage of 20 to 30 kV. Both solid and powder samples were prepared for both crystal plane and powder X-ray diffraction (XRD, Philips PANalytical X’Pert, Cu $K_{\alpha }$ wavelength). For peak identification and crystal structure Rigaku data analysis software (PDXL—version 2) was used. Part of the crystal was prepared via fracturing for Thermo-gravimetric analysis (TGA, TA Instruments Discovery SDT 650).