Crystallization of β-carotene by a GAS process in batch Effect of operating conditions

β-carotene has been successfully recrystallized from ethyl acetate and dichloromethane solutions using carbon dioxide as antisolvent in a batch bench plant for GAS process. The aim of this work is to study the influence of operating variables (concentration, temperature, stirring rate and type of solvent) and the efficiency of the GAS process on final size of the crystals. Crystals smaller than 1 μm are obtained at temperature of 298 K, pressure of 5.8 MPa, from 1 g/l solutions and with a stirring rate of 25 Hz. GAS process yields trans isomer with high efficiency separation. Solubility of β-carotene in CO₂ plus ethyl acetate at different temperatures (298, 313 and 333 K) from 4.3 to 9.8 MPa were measured, values ranged between 0.45 (P=7.2 MPa, T=333 K) and 0.010 g/l (P=8.1 MPa, T=313 K). In addition, distribution and size of the crystals from raw and recrystallized β-carotene for the CO₂–ethyl acetate system are studied.     

Effect of the solvent composition and annealing process on the preparation of spray freeze-dried acetaminophen powder

The analgesic and physical properties of acetaminophen powder suitable as an inhaled drug produced by spray freeze-drying (SFD) were compared with those of raw acetaminophen. A laser particle size analyzer and scanning electron microscopy (SEM) were applied to estimate physical structure and properties of the particles. A cyclooxygenase (COX) inhibitor screening assay was used to compare the antipyretic and analgesic activity of raw and SFD acetaminophen. According to SEM, SFD acetaminophen particles had various shapes and sizes with porous structures. The optimized conditions for solvent, annealing temperature, and annealing time were water/ethanol mixture (60% water and 40% ethanol), ?40°C, and 7?h, respectively. The diameter of optimized acetaminophen powder was 7.33?µm, and the aerodynamic particle size was 3.38?µm. The antipyretic and analgesic activities of acetaminophen after SFD were from 84.3 to 97.1% for COX-1 and from 91.6 to 102.9% for COX-2 compared to those of raw acetaminophen, respectively.     

Nanoencapsulation of Alpha-linolenic Acid with Modified Emulsion Diffusion Method

Nanocapsules of alpha-linolenic acid (α-LA) were prepared by a modified emulsion diffusion technique with encapsulation efficiency of 93%. Polylactic acid (PLA) was used as the encapsulating polymer with acetone and ethyl acetate as organic solvents, and Tween 20, gelatin and Pluronic-F68 in water as stabilizers. Two ratios of organic to aqueous phases were used with each solvent and stabilizer. Nanocapsule dispersions with a particle size less than 100 nm and a zeta potential as high as 33 mV were obtained as verified by scanning electron microscopy and the dynamic light scattering technique respectively. Both particle size and zeta potential were influenced by such preparation conditions as the type of stabilizer, type of organic solvent and the organic to aqueous phase ratio. Acetone was superior to ethyl acetate, and Tween 20 was superior to each of Pluronic-F68 and gelatin in obtaining smaller, less aggregated nanocapsules. An organic to aqueous phase ratio of 1:5 was shown to be more suitable for the formation of smaller nanocapsules, particularly when acetone was used as the organic solvent.     

Preparation of poly(L-lactic acid) submicron particles in aerosol solvent extraction system using supercritical carbon dioxide

The aerosol solvent extraction system process (ASES), which is one of the supercritical anti solvent processes (SAS), was used to produce poly(L-lactic acid) (PLLA) into the submicron particles. Dichloromethane (DCM, CH₂Cl₂) and carbon dioxide were selected as a solvent and as an antisolvent for PLLA, respectively. The objective of this study was to investigate the effect of the various process parameters such as temperature, pressure, and solution concentration on PLLA particles. With increasing temperature and pressure, particle size was increased. Also, higher PLLA concentration led to larger particle size and broader particle size distribution. A scanning electron microscope (SEM) was used to observe the morphology and size of PLLA particles recrystallized by ASES process. The mean particle size and its distribution of processed particles were measured by using a laser diffraction particle size analyzer (PSA).     

Application of Taguchi method in the optimization of dissolution of ulexite in NH4Cl Solutions

The Taguchi method was used to determine optimum conditions for the dissolution of ulexite in NH₄Cl solutions. The ranges of experimental parameters were between 50–87 ‡C for reaction temperature, 0.05-0.20 gmL^-1 for solid-to-liquid ratio, 1–4 M for NH₄Cl concentration, 5–25 min for reaction time, and (-850+600)-(-90) Μm for particle size. The optimum conditions for these parameters were found to be 87 ‡C, 0.05 gmL^-1, 4M, (-300+212) Μm, and 18 minutes, respectively. Under these conditions, the dissolution percentage of ulexite in NH₄Cl solution was 98.37. Reaction products were found to be boric acid, ammonium tetraborates, sodium tetraborate decahydrate, calcium chloride, and sodium chloride.     

Recrystallization of tetracycline hydrochloride using supercritical anti-solvent process

Tetracycline hydrochloride (TTC) was micronized by an Aerosol Solvent Extraction System (ASES) using supercritical CO₂. The effects of solvent, pressure and temperature of CO₂, solution concentration, and solution feed rate on particle size were investigated. Mean particle sizes of processed TTC were 0.16–0.31 μm, but the morphologies of processed particles were affected by agglomeration between the primary particles. Mean particle sizes of unprocessed TTC were ca. 200 μm and the shapes were irregular with rough surfaces. Especially, particle sizes increased from 0.18 to 0.31 μm as CO₂ temperature increased. In addition, particle sizes increased from 0.18 to 0.23 μm as TTC concentration increased. Powder X-Ray diffractometry revealed that processed particles were amorphous whereas unprocessed particles showed strong crystallinity.     

Powder coating efficiency of small particles and their agglomeration in circulating fluidized bed

The coating efficiency of fluidizing small particles and their agglomeration were investigated to evaluate the possibility of powder coating by the use of a circulating fluidized bed. Glass beads, whose mean diameter was 43 Μm, and silica powder of 1 Μm were used as a core and a coating material. Polyvinyl alcohol was used as a binder and its solution was supplied together with silica powder from a spray nozzle equipped in the circulating fluidized bed. Glass beads of 43 Μm, which had been impossible to coat in a conventional fluidized bed coater, were successfully coated with silica powder in a circulating fluidized bed, and agglomeration among core particles was prevented. From this result, it was confirmed that a circulating fluidized bed performs excellently as a coater, especially for fine core particles, so a circulating fluidized bed coater has bright prospects for particle coating.     

Supercritical anti-solvent micronization of chromatography purified marigold lutein using hexane and ethyl acetate solvent mixture

This work aims to study supercritical anti-solvent micronization of marigold derived purified lutein that was dissolved in the mixture of hexane and ethyl acetate (70:30 v/v), the solvent used as the mobile phase for chromatographic purification. The results show significant effect of pressure on the morphology of micronized lutein particles. The increase in lutein initial concentration from 1.5 mg/ml to 3.2 mg/ml and the increase in SC-CO₂ flow rate from 15 ml/min to 25 ml/min show no significant effects on the morphology of lutein particles. However, the reduction of mean particle size from about 2 μm to 0.8 μm was observed by increasing SC-CO₂ flow rate. The X-ray diffraction patterns of the micronized lutein particles show apparent amorphous nature, while the Fourier transform infrared spectroscopy results show that no chemical structural changes occurred. Moreover, the solubility of the micronized lutein particles in aqueous solution was found to increase significantly from being almost insoluble to having approximately 20% solubility     

Preparation and characterization of nifedipine-loaded cellulose acetate butyrate based microspheres and their controlled release behavior

Eudragit L100/cellulose acetate butyrate blend microspheres were prepared by solvent evaporation technique using poly(vinyl alcohol) as an emulsifying agent nifedipine (NFD) was successfully loaded into these microspheres. The effect of experimental variables such as ratio of blend ratio on NFD encapsulation efficiency, release rate, size, and morphology of the microspheres has been investigated. Scanning electron micrographs indicated the formation of spherical microspheres. Mean particle size of the microspheres has been measured by the laser light scattering technique ranged between 100 and 120 μm. NFD was successfully encapsulated up to 80% in the polymeric matrices. In vitro dissolution experiments performed in pH 7.4 buffer medium indicated a controlled release of NFD from the blend microspheres up to 12 h.     

Effect of solvent type on preparation of ethyl cellulose microparticles by solvent evaporation method with double emulsion system using focused beam reflectance measurement

The purpose of this study was to investigate the effect of solvent type on the solidification rate of ethyl cellulose (EC) microparticles and particle size/distribution of emulsion droplets/hardened microparticles during the solvent evaporation process using focused beam reflectance measurement (FBRM). EC microparticles were prepared with a water‐in‐oil‐in‐water solvent evaporation method using various solvents, including dichloromethane, dichloromethane–methanol (1:1), ethyl acetate and chloroform. The particle size/distribution of the emulsion droplets/hardened microparticles was monitored using FBRM. The morphology of EC microparticles was characterized using scanning electron microscopy (SEM). The transformation of the emulsion droplets into solid microparticles for all solvents occurred within the first 10–90 min. The square weighted mean chord length of EC microparticles prepared using chloroform was smallest, but the chord count was not the highest. The chord length distribution (CLD) measured by FBRM showed that a larger mean particle size gave longer CLD and a lower peak of particle number. SEM data revealed that the morphology of microparticles was influenced by the type of solvent. FBRM can be employed for online monitoring of the shift in the microparticle CLD and detect transformation of emulsion droplets into solid microparticles during the solvent evaporation process. The microparticle CLD and transformation process were strongly influenced by solvent type. © 2017 Society of Chemical Industry     

Precipitation of pharmaceuticals using a supercritical anti‐solvent (SAS) dechnique: A preliminary study

The aims of this research were to investigate the applicability of the supercritical anti‐solvent (SAS) process on the precipitation of pharmaceuticals (andrographolide and acetaminophen). In particular, the goal of this research was to study the influence of pressure at 10 and 24 MPa on particle characteristics (morphology, crystalline structure, polymorphic form, size, size distribution, and precipitation yield), and to compare the precipitation efficiency of SAS process and evaporation process. Scanning electron microscope (SEM), X‐ray diffraction (XRD), and high performance liquid chromatography (HPLC) showed a significant change in particle size, size distribution, morphology, and precipitation yield, respectively. From an analysis of the results it was found that the crystal size of andrographolide and acetaminophen decreased with increasing pressure. The morphology of andrographolide particles changed from slice‐like to column‐like when the pressure was increased. On the other hand, the acetaminophen particles obtained were found to be monoclinic form (I) under both operating pressures. The SAS process produced small uniform shaped crystals, with a narrow size distribution, high precipitation yield and selective precipitation were also observed.     

High-pressure liquid chromatography and ultraviolet spectrometry of ketonic C27 sterols

A method for the separation of ketonic C₂₇ sterols was devised, based on high-pressure liquid chromatography (HPLC) and ultraviolet absorption (UV). The adsorption column contained silica gel, particle size 10 μm, and the eluents were dichloromethane/n-hexane/ethyl acetate (94∶5∶1) and dichloromethane/ethyl actate (99∶1) followed by dichloromethane/ethyl acetate (3∶1). The 5β-sterols were eluted before the 5α-analogs, sterols with isolated double bonds before conjugated carbonyl compounds, and ketones before hydroxy ketones. The effect of carbonyl groups on polarity depends on the position in the molecule and decreases in the order C-3>C-6>C-7. The ultraviolet absorption spectra of eleven sterols were determined, and their absorbance at 254 nm and at 280 nm was used for analyzing the column effluent with a dual detector system. Plant Biochemistry Research Unit. Instrumental Analysis Research Unit. Reference to a company and/or product named by the Department is only for purposes of information and does not imply approval or recommendation of the product to the exclusion of others which may also be suitable.     

Recrystallization of erlotinib hydrochloride and fulvestrant using supercritical antisolvent process

Recrystallization of two anti-cancer active pharmaceutical ingredients (APIs), erlotinib hydrochloride (erlotinib HCl) and fulvestrant, using supercritical antisolvent (SAS) process was investigated in this study. The most commonly used supercritical carbon dioxide was employed as the antisolvent. Effect of three process parameters including the operating temperature, pressure and solution flow rate have been studied. Analyses of the recrystallized erlotinib HCl and fulvestrant were examined by SEM, XRD and DSC. Erlotinib HCl was recrystallized from its mean particle size of 20 μm to 2 μm with different crystal habits. Different polymorphs of erlotinib HCl were obtained and confirmed from the XRD and DSC results. The prior art polymorph form A of erlotinib HCl showed enhanced dissolution rate by 3.6 times to its original polymorph form B. Significant particle size reduction was also obtained for fulvestrant. The mean particle size was reduced from its original value of 22 μm to 2 μm with much narrower particle size distribution. The cross-interaction effect between the operating temperature and pressure observed in the SAS treatment of fulvestrant was verified by the method of calculated mixture critical point (MCP). The micronized fulvestrant particles showed consistent polymorph as the original API, but with different crystal habits. It is confirmed that the SAS method is applicable for controlling the crystal properties of two APIs, erlotinib HCl and fulvestrant, which require rigorous control of physical characteristics.     

乙基纤维素-艾叶粉溶液微胶囊的制备

文章首次以乙基纡维素为壁材,采用溶剂蒸发法制得艾叶粉水溶液微胶囊。正交实验得出制备微胶囊的最佳工艺条件为：乙基纤维素：芯材：乙酸乙酯：水相=1：25：13：130（质量比）,搅拌速度：1500r／min,乳化时间：15mim,水油两相混合搅拌时间：10min。通过扫描电镜表征结果显示,所得微胶囊固体颗粒呈球形,分散性好,粒径在20-200μm范围内。实验制得微胶囊最大载药量为48．07％,具有良好的包覆效果。透析缓释实验表明,微胶囊在3.0℃恒温生理盐水浸泡60h后,仍有艾叶药理活性成分存在,较好地延长了储藏时间和药物有效作用时限。     

Separation of perillyl alcohol from the peel of citrus unshiu by supercritical CO2 and preparative high-performance liquid chromatography

To separate perillyl alcohol (POH), a potential anti-cancer agent, the peel of citrus unshiu was extracted by supercritical CO₂ extraction (SCE) system at 50 ‡C, 200 bar and 6 kg CO₂/hr/kg sample. The extracts were partitioned by acetonitrile/hexane (90/10, vol%). POH was eluted in the acetonitrile phase. An open-tubular chromatography with silica gel (40–63 Μm) was used to purify POH from the acetonitrile phase. Mobile phase was hexane/ethyl acetate (90/10, vol%). To obtain POH in a pure form, finally preparative high-performance liquid chromatography was applied. The collection of POH from citrus unshiu peel was achieved on a laboratory-prepared Chromatographic column (300x3.9 mm) packed with 15 Μm C₁₈ preparative packings. The composition of mobile phase was water/acetonitrile (50/50, vol%). The flow rate of the mobile phase was 1 ml/min and UV wavelength was fixed at 205 nm. It was found that the total yield of POH was 1.6xl0^-3 (wt%) as the dry powder of citrus unshiu peel.     

Axial gas dispersion in a fluidized bed of polyethylene particles

Gas mixing behavior was investigated in a residence time distribution experiment in a bubbling fluidized bed of 0.07 m ID and 0.80 m high. Linear low density polyethylene (LLDPE) particles having a mean diameter of 772 Μm and a particle size range of 200-1,500 Μm were employed as the bed material. The stimulus-response technique with CO₂ as a tracer gas was performed for the RTD study. The effects of gas velocity, aspect ratio (H₀/D) and scale-up on the axial gas dispersion were determined from the unsteady-state dispersion model, and the residence time distributions of gas in the fluidized bed were compared with the ideal reactors. It was found that axial dispersion depends on the gas velocity and aspect ratio of the bed. The dimensionless dispersion coefficient was correlated with Reynolds number and aspect ratio.     

Supercritical anti-solvent micronization of marigold-derived lutein dissolved in dichloromethane and ethanol

This work aims to study supercritical anti-solvent (SAS) micronization of lutein derived from marigold flowers. Lutein solution in dichloromethane (DCM) or ethanol was atomized into the stream of supercritical carbon dioxide (SC-CO₂) through a concentric nozzle in a pressurized vessel. The effects of pressure and SC-CO₂ flow rate on morphology, mean particle size (MPS) and particle size distribution (PSD) were investigated. The reduction in lutein MPS from 202.3 μm of unprocessed lutein to 1.58 μm and 902 nm could be achieved by SAS micronization using DCM and ethanol, respectively. In both solvent systems, no significant effects of pressure and SC-CO₂ flow rate on particle morphology were observed. However, pressure was found to have a significant effect on MPS and PSDs of lutein particles.     

Preparation of ethyl cellulose microcapsules containing perphenazine and polymeric perphenazine based on acryloyl chloride for physical and chemical studies of drug release control

The preparation of microcapsules containing perphenazine by solvent evaporation using ethyl cellulose is described. The microparticles are formed after solvent evaporation and polymer precipitation. The drug was dissolved in a polymer solution and emulsified into an aqueous phase to form microcapsules. To study the effects on particle size, encapsulation efficiency and morphology, three different molecular weights of ethyl cellulose (M_w=47000, 71000 and 99000) were used. Covalent bonding of drugs to polymers via hydrolytically or enzymatically cleavable covalent bond was achieved for sustained drug delivery. The release rate of perphenazine from these systems was investigated. © 1998 Society of Chemical Industry     

Preparation of ferroelectric Pb(Zr0.52 Ti0.48)O3 thin films by sol-gel processing

Ferroelectric Pb(Zr_0.52 Ti_0.48)O₃ thin films were prepared by sol-gel processing on the Pt/Ti/SiO₂/Si(100) substrates. Effects of the concentration (0.2–0.8 M) of the starting solution (Pb/Zr/Ti= 1.1/0.52/0.48) and the sintering temperature (500–700 ‡C) on crystallinity, microstructure and electrical properties of PZT thin films were investigated. For the thin film prepared at 0.4 M starting solution, the highest crystallinity appeared at a sintering temperature of 650 ‡C. The average grain size of the PZT thin films was about 0.17 Μm. The film thickness was about 0.2 Μm. The relative dielectric constant and the dissipation factor of the film measured at 1 kHz were about 750 and 4.3%, respectively. The remnant polarization (Pr) and coercive field (Ec) of the film measured at the applied voltage of 5 V were about 49 ΜC/cm² and 134 kV/cm, respectively.     

Size-dependent luminescent properties of hollow and dense BaMgAl<Subscript>10</Subscript>O<Subscript>17</Subscript>: Eu blue phosphor particles prepared by spray pyrolysis

Hollow and dense BaMgAl10O17: Eu₂₊ (BAM) phosphor particles were synthesized by a spray pyrolysis process and their luminescent properties were investigated under vacuum ultraviolet (VUV) excitation as varying the average particle size. The dependence of the luminescent intensity on the particle size was greatly influenced by the morphology of BAM particles. For the BAM particles with a hollow structure, the luminescent intensity linearly increased with increasing the particle size. However, no significant change in the luminescent intensity was observed for dense particles as the particle size changed. Also, all dense BAM particles had higher photoluminescence intensity than that of the hollow ones regardless of the particle size. The luminescent intensity of BAM phosphor particles prepared by spray pyrolysis was found to have a linear relationship with the crystallite size. Therefore, it was concluded that suppressing the formation of a hollow structure and increasing the crystallite size are needed to obtain high luminous BAM phosphor particles with a spherical shape and fine size of less than 1 Μm. On the basis of penetration depth of VUV, a simple relation equation between the particle size and the luminescent intensity was derived and correlated with experimental results in order to interpret the luminescent behavior of BAM phosphor as the particle size changes.