Recrystallization of phenylbutazone using supercritical fluid antisolvent process

Phenylbutazone was recrystallized from its solutions by using a supercritical fluid antisolvent process. It was dissolved in acetone and supercritical carbon dioxide was injected into the solution, thereby inducing supersaturation and particle formation. Variation in the physical properties of the recrystallized phenylbutazone was investigated as a function of the crystallizing temperature and the carbon dioxide injection rate. The recrystallized particles showed cleaner surfaces and more ordered morphology compared to the particles obtained by other methods such as solvent evaporation. X-ray diffraction patterns indicated that the crystallinity of the particles had been modified upon the recrystallization. Differential scanning calorimetry measurement revealed that the crystallizing temperature influenced the thermal stability of the resulting crystals. Larger crystals were produced when the carbon dioxide injection rate was reduced.     

Preparation and Characterization of Taxifolin Form II by Antisolvent Recrystallization

To improve the aqueous solubility and dissolution rate of taxifolin, taxifolin form II was successfully prepared through antisolvent recrystallization, in which 1‐butyl‐3‐methylimidazolium tetrafluoroborate and dichloromethane were used as solvent and antisolvent, respectively. The properties of taxifolin form II were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X‐ray diffraction, differential scanning calorimetry, solid‐state NMR spectroscopy, the dissolving capability test, and the bioavailability test. The chemical structure of taxifolin form II was not changed, but its morphology and crystalline structure changed during the recrystallization process. Moreover, taxifolin form II showed higher solubility, faster dissolution rate, and better bioavailability than taxifolin form I.     

Preparation of Aqueous Nanodispersions of Disperse Dye by High-Gravity Technology and Spray Drying

Disperse dyes are poorly water-soluble and difficult to stably disperse in an aqueous medium, which greatly limits their application in dyeing synthetic fibers. Micronization can solve this problem. Herein, a facile way to prepare stable aqueous nanodispersions of disperse dye (C.I. disperse yellow 54) is presented by combining high-gravity antisolvent precipitation in a rotating packed bed (RPB) with spray drying. The as-prepared product had an average particle size of 120 nm, which could be readily redispersed in water. Compared with raw dye, the wettability and dispersibility of disperse dye nanoparticles were remarkably improved. Furthermore, the dyeing properties of the nanodispersions were obviously better than those of the commercial dye, which was micronized by ball milling.     

A new system for particle formation using the principle of the SAS process: The Concentric Tube Antisolvent Reactor (CTAR)

This paper presents a new system to produce micrometric narrow size distribution particles. The principle is the same as for a conventional supercritical antisolvent process (SAS), with the contact of the organic solution containing the solute to be precipitated and the supercritical CO₂ playing the role of an antisolvent. This paper exposes the functioning of the system used for the contact of the two phases. It is constituted by two concentric tubes; an external one partially for the CO₂ and an internal one for the organic solution. Its name is the Concentric Tube Antisolvent Reactor (CTAR). This system is a compacted and simple one. It has been tested with a usual polymer (l-poly lactic acid) often processed by the use of the SAS methods. Different experiments have shown that this system is convenient for the production of particles, leading to almost equivalent results as in other processes with identical operating conditions. There are still remaining problems for the recovery of the powder formed, which is usual for this kind of process. This system could be very useful for the scaling up of the process, by multiplying the number of tubes with an easy permanent control on the operating conditions. Some improvements have been made for operating parameters, as the concentration of LPLA in the organic solution and the molar ratio solvent/supercritical CO₂ that can be processed.     

Antisolvent crystallization: Model identification, experimental validation and dynamic simulation

This paper is concerned with the development, simulation and experimental validation of a detailed antisolvent crystallization model. A population balance approach is adopted to describe the dynamic change of particle size in crystallization processes under the effect of antisolvent addition. Maximum likelihood method is used to identify the nucleation and growth kinetic models using data derived from controlled experiments. The model is then validated experimentally under a new solvent feedrate profile and showed to be in good agreement. The resulting model is directly exploited to understand antisolvent crystallization behavior under varying antisolvent feeding profiles. More significantly, the model is proposed for the subsequent step of model-based optimization to readily develop optimal antisolvent feeding recipes attractive for pharmaceutical and chemicals crystallization operations.     

Preparation of L-PLA submicron particles by a continuous supercritical antisolvent precipitation process

Submicron particles of L-polylactic acid (L-PLA) without residual solvent were prepared by a continuous supercritical antisolvent (SAS) recrystallization process. Methylene chloride (CH₂C1₂) was used as a carrier solvent of L-PLA. Experiments were performed with changing process parameters such as pressure and temperature at constant concentration. Also, L-PLA initial concentrations in methylene chloride were varied from 0.3 to 4 wt%. The flow rates of CO₂ and solution, which were introduced into the precipitator, and nozzle diameter were kept unchanged in all of the experiments. It was found that the SAS process gives fine tuning of particle size and particle size distribution (PSD) by simple manipulations of the process parameters. In all cases of SAS recrystallization experiments, the formed spherical fine particles with a smooth surface were non-agglomerated and free flowing. Mean particle size of the L-PLA microparticles formed was varied from 0.1 to 1 μm by means of adjusting the system pressure and/or temperature.     

Preparation and properties of optoelectronic conversion films of perovskite modified by octadecyl-trichloro silane

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Antisolvent crystallization of carbamazepine from organic solutions

Carbamazepine was crystallized from organic solutions using an antisolvent crystallization technique. Ethanol was used as a solvent for the carbamazepine and distilled water was used as an antisolvent. The carbamazepine was dissolved in the solvent, and the drug solution was injected into the antisolvent causing the particle precipitation. During the crystallization experiments, the effects of the process parameters such as solution concentration, temperature, injection rate of the solution, and the presence of ultrasound, were investigated. An analysis of the produced particles showed that external characteristics such as particle size and its distribution were a strong function of the process parameters, while the internal structures such as crystallinity and thermal stability were nearly unaffected. Smaller particles were obtained when solutions with high drug concentrations were used. Higher temperature resulted in larger crystals. Particle size was also influenced by the injection rate of the drug solutions. Carbamazepine particle size was significantly reduced when the ultrasonic wave was selectively applied.     

Preparation of polystyrene/poly(methyl methacrylate) blends by compressed fluid antisolvent technique

Submicron polystyrene (PS)/poly(methyl methacrylate) (PMMA) blends were generated by the precipitation with a compressed antisolvent (PCA) technique. The generation of PS/PMMA blends was carried out by spraying a solution containing PS and PMMA into a precipitator. The blends without coalescence were observed to only be generated when both vapor and liquid CO₂ existed in the precipitator combined with appropriate total polymer concentration in solution, molecular weights (Mws) of PS and PMMA, mass ratio of PS to PMMA, flow rates of CO₂ and polymer solution, and liquid CO₂ level in the precipitator. Two Mws of PS, 144,000 and 44,000, and two Mws of PMMA, 85,000 and 36,000, were used in this study. It was found that the blends could be easier to generate using a higher PS Mw, a lower PMMA Mw, and a higher mass ratio of PS to PMMA. Toluene with a solubility parameter smaller than that of tetrahydrofuran (THF) was found to be the more appropriate solvent for generating spherical PS/PMMA submicron blends. The SEM and TEM images show that the spherical PS/PMMA core/shell blends could be generated at a temperature of 298 K, a pressure of 6.41 MPa, a liquid CO₂ level of 1/2 of the precipitator, a CO₂ flow rate of 2000 mL/min, a solution flow rate of 5 or 10 mL/min, and a total polymer concentration of 0.72 wt% for a PS Mw of 144,000, a PMMA Mw of 36,000, and a PS/PMMA mass ratio of 9/1. Individual and spherical PS and PMMA particles or spherical PS particles partially covered by a PMMA films, however, were generated when the liquid CO₂ level was of 1/8 or lower in the precipitator. A possible mechanism for the formation of core-shell blend was proposed.     

A new approach to select solvents and operating conditions for supercritical antisolvent precipitation processes by using solubility parameter and group contribution methods

A new approach is proposed to select operating temperature and pressure for supercritical antisolvent particle precipitation based on solubility parameter calculated by group contribution methods and using only the critical properties of the solvent. Solubility parameters are also used to choose the most suitable organic solvent for a given application. Supercritical antisolvent precipitation operating conditions of 36 systems are investigated including 8 organic solvents (methanol, ethanol, acetone, DMSO, DCM, chloroform, NMP and acetic acid) and 6 solid solutes (atenolol, tartaric acid, flunisolide, paracetamol, amoxicillin and cholesterol) in the temperature and pressure ranges of 25⿿85 °C and 50⿿250 bar. The results show a good agreement between the experimental and calculated data for these systems. Although particle precipitation depends on several parameters such as mass-transfer rates and hydrodynamics, the focus of this work is on the role of thermodynamics to indicate the preliminary conditions for a successful antisolvent precipitation process. Validation and results of this new approach suggest that it can be a useful tool for a qualitative and completely predictive evaluation of supercritical antisolvent particle precipitation in a cheaper way than carrying out experimental runs.