Zhigang Shen

Micronization of atorvastatin calcium by antisolvent precipitation process

Amorphous atorvastatin calcium (AC) ultrafine powder has been successfully prepared by antisolvent precipitation and spray drying process, in which hydroxypropyl methylcellulose (HPMC) was employed to control the particle size and morphology. The effects of experimental parameters, such as stirring time, drug concentration and drying methods, on particle size and morphology were investigated. The average particle size of AC obviously increased from 410 nm to 1200 nm as the stirring time changed from 30s to 60 min. The enhancement of drug concentration favored to decrease the particle size from 410 nm to 240 nm. After spray drying process, ultrafine AC powder was obtained, which had good dispersibility and narrow particle size distribution of 1-3 microm. The as-prepared ultrafine AC was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, thermal gravimetric analysis (TG), differential scanning calorimetry (DSC), specific surface area and dissolution test. The XRD analyses indicated that the ultrafine AC was amorphous. In the dissolution tests, the amorphous AC ultrafine powder exhibited enhanced dissolution property when compared to the raw material.

Determination of pore size distribution and adsorption of methane and CCl4 on activated carbon by molecular simulation

A combined method of grand canonical Monte Carlo (GCMC) simulation and statistics integral equation (SIE) for the determination of pore size distribution (PSD) is developed based on the experimental adsorption data of methane on activated carbon at ambient temperature, T=299 K. In the GCMC simulation, methane is modeled as a Lennord–Jones spherical molecule, and the activated carbon pore is described as slit-shaped with the PSD. The well-known Steele’s 10-4-3 potential is used to represent the interaction between the fluid molecule and the solid wall. Covering the range of pore sizes of the activated carbon, a series of adsorption isotherms of methane in several uniform pores were obtained from GCMC. In order to improve the agreement between the experimental data and simulation results, the PSD is calculated by means of an adaptable procedure of deconvolution of the SIE method. Based on the simulated results, we use the activated carbon with the PSD as the prototype of adsorbent to investigate adsorption. The adsorption isotherms of methane and CCl4 at 299 K in the activated carbon with the PSD are obtained. The adsorption amount of CCl4 reaches 20 mmol/g at ambient temperature and pressure. The results indicate that the combined method of GCMC and SIE proposed here is a powerful technique for calculating the PSD of activated carbons and predicting adsorption on activated carbons.

Facile Preparation of Danazol Nanoparticles by High-Gravity Anti-solvent Precipitation (HGAP) Method

The nanoparticles of the hydrophobic drug of danazol with narrow size distribution are facilely prepared by controlled high-gravity anti-solvent precipitation (HGAP) process. Intensified micromixing and uniform nucleation environment are created by the high-gravity equipment (rotating packed bed) in carrying out the anti-solvent precipitation process to produce nanoparticles. The average particle size decreases from 55μm of the raw danazol to190nm of the nanoparticles. The Brunauer-Emmett-Teller (BET) surface area sharply increases from 0.66m^2•g^(-1) to 15.08 m^2g^(-1). Accordingly， the dissolution rate is greatly improved. The molecular state, chemical composition, and crystal form of the danazol nanoparticles remains unchanged after processing according to Fourier transform infrared (FTIR) and X-ray diffraction (XRD). The high recovery ratio and continuous production capacity are highly appreciated in industry. Therefore, the HOAP method might offer a general and facile platforrI1 for mass production of hydrophobic pharmaceutical danazol particles in nanometer range.

Micronization of silybin by the emulsion solvent diffusion method.

Micronized silybin particles were successfully prepared by emulsion solvent diffusion method. Uniform spherical and rod-shaped particles with a mean size of 2.48 and 0.89 microm could be obtained using sodium dodecyl sulfate (SDS) concentration of 0.1 wt% at 30 and 15 degrees C, respectively. The characterization of silybin particles by SEM and particle size distribution (PSD) indicated that with the increase of temperature from 15 to 30 degrees C, the as-prepared particles became bigger and had a tendency to turn into spherical shapes; with the increase of SDS concentration from 0.02 to 0.1 wt%, the span of PSD became narrower while the mean particle size kept almost unchanged. XRD patterns and FT-IR spectra showed that the spherical and rod-shaped silybin particles possessed decreased crystallinity; however, the chemical structure and components were similar to those of the commercial silybin powder. Dissolution tests demonstrated that both of the spherical and rod-shaped silybin particles exhibited significantly enhanced dissolution rate when compared to the commercial silybin powder.

Nanosized bicalutamide and its molecular structure in solvents

Nanosized bicalutamide particles have been obtained by anti-solvent precipitation after screened DMSO and EtOH as co-solvents. The produced nanoparticles have been characterized by scanning electron microscopy (SEM), Fourier transform infrared spectrophotometry (FTIR), X-ray diffraction (XRD) and a dissolution test. The mean particle size of bicalutamide is about 450nm with a narrow distribution. The results of the dissolution test show that dissolution rate of the produced nanoparticles are higher than that of the raw material. Besides, DFT calculations of the bicalutamide conformers have firstly been presented. It is found that the calculated geometry structure of lower-energy conformer is very similar to the experimental structure existing within the crystal lattice. The solvent effects have been taken into account based on the polarizable continuum model (PCM). The computed results appear that the introduction of dielectric medium has obvious effect on the molecular geometry of bicalutamide.

Preparation of ultrafine fenofibrate powder by solidification process from emulsion

The solidification process from emulsion, which consisted of emulsifier, water and molten drug as oil phase without use of any organic solvent, was firstly employed to prepare ultrafine fenofibrate (FF) powder. The effects of stirring speed and volume ratios of hot emulsion to cold water on the particle size and morphology were discussed as well as the impacts of different emulsifiers on emulsion. The produced ultrafine powder was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, specific surface area analysis and a dissolution test. XRD patterns and FT-IR spectra showed that the ultrafine FF was crystalline powder with the structure and the components similar to those of bulk drug. The product had a mean particle size of about 3 microm with a narrow distribution from 1 microm to 5 microm. The specific surface area reached up to 6.23 m(2)/g, which was about 25 folds as large as that of bulk FF. In the dissolution tests, about 96.1% of ultrafine FF was dissolved after 120 min, while there was only 38.1% of bulk drug dissolved, proving that the dissolution property of ultrafine FF was significantly improved when compared to commercial drug.

Micronization of gemfibrozil by reactive precipitation process

Ultrafine gemfibrozil (GEM) was prepared by reactive precipitation process in which methyl cellulose (MC) was employed to inhibit the growth and the agglomeration of particles. The impact of NaOH concentrations on bulk GEM consumption was explored. The effects of H2SO4 concentrations and the drying methods on the particle size and morphology were also discussed. The produced ultrafine powders were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, specific surface area analysis and dissolution test. XRD patterns and FT-IR spectra showed that the as-obtained ultrafine GEM was a crystalline powder with the structure and components similar to those of bulk GEM. The ultrafine GEM had a mean particle size of about 1.25 microm with a narrow distribution from 0.6 to 3 microm. The specific surface area reached up to 11.01 m2/g, which was about 6 times as large as that of bulk GEM. In the dissolution tests, about 91.2% of ultrafine GEM was dissolved after 120 min, while there was only 23.6% of bulk GEM dissolved, proving that the dissolution property of ultrafine GEM was significantly enhanced when compared to commercial GEM owing to a decreased particle size and an increased specific surface area.

Low Temperature One Step Synthesis of Barium Titanate: Particle Formation Mechanism and Large-scale Synthesis

Abstract The formation of BaTiO3 nanoparticles via the reaction of BaCl2, TiCL4 and NaOH in aqueous solution has been systematically studied. The formation of BaTiO3 from the ionic precursors has been elucidated to be a very rapid process, occurring at temperature higher than 60°C. Furthermore, the particle size could be controlled by the proper selection of the synthesis conditions (e.g. reactant concentration of 0.5–1.0mol·L−1, temperature of 80–95°C and pH≥13). A two-step precipitation mechanism was proposed. The first stage of the synthesis involved the formation of amorphous Ti-rich gel phase. The second stage of the synthesis was the reaction between the amorphous phase and the solution-based Ba2+ ions, which led to the crystallization of BaTiO3. Based on the particle formation mechanism, a novel method, high gravity reactive precipitation, was proposed and used to mass production of BaTiO3 of average particle size of about 60 nm and with narrow particle size distribution. Because it could break up the amorphous Ti-rich gel into small pieces, intensify mass transfer, promote the reaction rate of amorphous Ti-rich gel with Ba2+ ions.

Fabrication of inhalable spore like pharmaceutical particles for deep lung deposition.

An innovative strategy of fabricating uniform spore like drug particles to improve pulmonary drug delivery efficiency was disclosed in the present study. Spore like particles were prepared through combination of high gravity controlled precipitation and spray drying process with insulin as model drug first, showing rough surface and hollow core. The shell of such spore-like particle was composed of nanoparticles in loose agglomerate and could form nanosuspension upon contacting antisolvent. Further characterization confirmed secondary structure and bio-activity was well preserved in spore like particles of insulin. Stable aerosol performance at different dosages with fine powder fraction (FPF) of 80% and comparable FPF (69-76%) for formulated powder were achieved, significantly higher than marketed product Exubera. On the other hand spore like particles of bovine serum albumin, lysozyme and salbutamol sulfate showed similar high FPF of 80%, regardless of different shape of primary nanoparticles, indicating various application of this new process in significant improvement of pulmonary drug delivery.

Transparent dispersion of nanoparticles and applications to fabricate advanced organic-inorganic composites

How to disperse the inorganic nanoparticles mono-uniformly in the organic matrices is the key challenge of innovation of new generation of organic-inorganic nanocomposites. In this paper, a simple strategic method by incorporating the transparent dispersion of nanoparticles into organic matrix was proposed to prepare transparent organic-inorganic nanocomposites. The transparent dispersions of nanoparticles in liquid solvents were synthesized by our proposed novel high-gravity reaction coupled with extraction-phase transfer (HGRT) technology. By such strategy, the various transparent organic-inorganic nanocomposites with unique functions were fabricated, where the inorganic nanoparticles were all dispersed at the nano-scale. The preparation process principle, scale-up operations and the properties of functional transparent nanoparticle dispersions as well as their applications in the innovation of nanocomposite films for glass energy-saving, nano-lubrications for high railways, advanced transparent flexible optical nanomaterials with the high content of nanoparticles (60 wt%) were reviewed.