Evaluation of Ultrasonic Treatment for the Size Reduction of HNS and HMX in Comparison to Solvent‐Antisolvent Crystallization

The paper presents and compares two methods for the synthesis of fine particles of the high explosives HNS and HMX by ultrasonic treatment and solvent/antisolvent crystallization. The effect of ultrasonic treatment on the particle size of explosives was studied by varying the amplitude and frequency of ultrasonication for different time periods using an ultrasonic probe and an ultrasonic bath. Solvent/antisolvent recrystallization was performed by varying the process parameters including stirring rate, antisolvent temperature etc. In addition to FT‐IR spectroscopy and thermal analysis by TGA/DSC; the particle size and shape of fine powders of the explosives HMX and HNS were determined using particle size analysis and scanning electron microscopy (SEM). Ultrasonic treatment of the probes resulted in the finer grains of HMX compared to solvent‐antisolvent crystallization. However in the case of HNS, solvent‐antisolvent crystallization produced finer particles compared to ultrasonication.     

Study on Preparation of Insensitive and Spherical High Bulk Density Nitroguanidine with Controllable Particle Size

In this study, the solventing‐out recrystallization method was applied to prepare insensitive and spherical high bulk density nitroguanidine (NQ). Experiments were performed at various operating conditions by using N‐methyl‐pyrrolidone (NMP) and acetone as solvent and antisolvent, respectively. The effects of different operating parameters such as NQ/NMP ratio, amount of acetone used, crystallization temperature, stirring speed and stirring time were investigated. The particle size and morphology of the prepared NQ crystals were observed by scanning electron microscopy (SEM), the bulk density was measured by the Archimedes’ method and the impact sensitivity was determined by fall hammer method. The experimental results showed that the solventing‐out recrystallization method could be used to prepare spherical high bulk density NQ with a narrow particle size distribution and the particle size could be controlled by changing the operating conditions. The bulk density of these spherical NQ particles was found to be in the range of 0.94–0.97 g cm⁻³, which is higher than that of needle‐shaped NQ particles, and they became less sensitive towards impact.     

Formation of biodegradable polymeric fine particles by supercritical antisolvent precipitation process

The supercritical antisolvent (SAS) precipitation process as a “green” alternative to specialty particles recrystallization was successfully used to generate poly(L ‐lactide) acid (L‐PLA) from dichloromethane (DCM) solution using CO₂ as antisolvent. The influence of main operating parameters on the synthesis of L‐PLA particles in the SAS process was methodically examined. In particular, antisolvent addition rate (30, 40, 50, and 60 g/min), temperature (35, 40°C, 45°C, and 50°C), solute concentration (50, 75, 100, and 150 mg/10 ml), and solution addition rate (1, 2.5, 5, and 7.5 ml/min). These parameters could be tuned to give a mean particle diameter of 0.62 μm. It was found using scanning electron microscopy and laser diffraction that increasing the antisolvent addition rate and the solution addition rate, while decreasing the temperature and solute concentration, led to a decrease in the L‐PLA mean particle diameter. Furthermore, a unimodal particle size distribution was obtained at the higher solution and antisolvent addition rates. Spherical‐like primary particles have been obtained in all the experimental runs; thus, no change of particle morphology with the process parameters has been noticed. These results manifested that SAS recrystallization process is a valuable technique to generate reproducibly polymer particles with controlled size and size distribution. POLYM. ENG. SCI. 2013. © 2012 Society of Plastics Engineers     

Preparation and characterization of cyhalothrin‐loaded poly(2‐hydroxyethyl methacrylate)‐co‐polylactide (PHEMA‐co‐PLA) ultrafine particles

Poly(2‐hydroxyethyl methacrylate)‐co‐polylactide (PHEMA‐co‐PLA) and its corresponding cyhalothrin‐loaded ultrafine particles were successfully synthesized and prepared, respectively. The chemical structures of the copolymers have been confirmed by Fourier transform infrared spectroscopy (FTIR), ¹H‐nuclear magnetic resonance (¹H‐NMR), ¹³C‐nuclear magnetic resonance (¹³C‐NMR), and thermogravimetric analysis (TGA). Furthermore, the particle size, the cyhalothrin loading content (LC), and the cyhalothrin release behavior were investigated. PHEMA‐co‐PLA proved to be a good material for the preparation of ultrafine particles for lipophilic pesticide delivery. The developed cyhalothrin‐loaded PHEMA‐co‐PLA ultrafine particles showed good dispersity in water and sustained release behavior. In addition, it is easy to be prepared by both nanoprecipitation method and emulsion/solvent evaporation method. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Recrystallization of Salicylamide using a Batch Supercritical Antisolvent Process

Recrystallization of the nonsteroidal anti‐inflammatory drug salicylamide was investigated using a batch supercritical antisolvent (SAS) precipitation process. Carbon dioxide was used as the antisolvent, and acetone, ethanol and ethyl acetate were used as solvents. Particle morphology determined by SEM showed that particles with a regular shape were obtained from the SAS process. The crystal structure analyzed by XRD showed that the intensities of specific peaks were modified. No decomposition or deterioration was confirmed by DSC measurements where the melting temperature remained the same after SAS recrystallization. The effects of process parameters were investigated with acetone as the solvent. At a higher pressure of 110 bar, a higher saturation concentration of 90 %, and a lower temperature of 293 K, the length of the rectangular particles decreased to 50 μm. This showed a significant change from the irregular and broken particle shapes with particle sizes up to 200 μm before processing by SAS.     

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).     

Liquid Antisolvent Recrystallization of Phenylbutazone and the Effect of Process Parameters

Phenylbutazone was crystallized from solutions by the liquid antisolvent recrystallization technique. Acetone was used as a solvent, and distilled water was selected as an antisolvent. The influence of processing parameters, such as drug concentration, temperature, injection rate of drug solution, and mixing method of drug solution with antisolvent, on the particle size distribution were investigated. Furthermore, to examine the variation of resulting particle size in the presence of the ultrasound, the ultrasonic wave was applied to all experiments. Larger crystals were obtained when crystallization took place at higher temperatures. The enhancement of drug concentration favored decreased particle size. Regarding the mixing method of the drug solution and antisolvent, smaller particles were produced when the drug solution was injected into antisolvent, and larger crystals were obtained when the antisolvent was injected into drug solutions. As the injection rate of the drug solution increased, the average particle size decreased. The processed particles consistently exhibited an acicular crystal habit. The presence of ultrasound caused a reduction of particle size under all operational conditions.     

Solvent effect on particle morphology in recrystallization of HMX (cyclotetramethylenetetranitramine) using supercritical carbon dioxide as antisolvent

Supercritical fluid processes have gained great attention as a new and environmentally benign method of preparing the microparticles of energetic materials like explosives and propellants. In this work, HMX (cyclotetramethylenetetranitramine) was selected as a target explosive. The microparticle formation of HMX using supercritical antisolvent (SAS) recrystallization process was performed and the effect of organic solvent on the size and morphology of prepared particles was observed. The organic solvents used in this work were dimethylsulfoxide (DMSO), N,N-dimethylformamide (DMF), cyclohexanone, acetone, and N-methyl pyrrolidone (NMP).     

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.     

反溶剂重结晶法制备青蒿素超细粉体

采用反溶剂重结晶法进行了青蒿素超细粉体的制备研究。以乙醇为溶剂,水为反溶剂,系统考察了药用辅料类型、反溶剂溶剂体积比、药物溶液浓度和混合强度对产品颗粒形貌和大小的影响。结果表明,辅料羟丙甲纤维素(HPMC)与聚乙烯吡咯烷酮 (PVP)联用可有效控制颗粒形貌,反溶剂溶剂体积比为20,青蒿素乙醇溶液浓度为20 mg·ml^-1,搅拌转速为8000 r·min^-1时,浆料中可得到平均短径0.84 μm、长径3 μm的针状颗粒,此浆料经喷雾干燥可得到粒径为2～3 μm的类球形粉体颗粒。进一步采用红外光谱、X射线衍射、差热分析、比表面积测试对原料药及产品的特性进行了表征,结果显示,青蒿素经反溶剂重结晶过程与辅料HPMC间产生一定的氢键作用,超细粉体产品的结晶度及熔点降低,比表面积增至原料药的26.4倍。体外溶出测试结果表明,青蒿素超细粉体的溶出速率远优于原料药,超细药物粉体15 min即可溶出88.3%,而同期原料药的溶出度仅为2.1%。     

Pressurized Nozzle‐Based Solvent/Anti‐Solvent Process for Making Ultrafine ϵ‐CL‐20 Explosive

CL‐20 explosive is one of the most recent and powerful explosives. It has very high potential in futuristic applications but at present it has limitations of sensitivity to mechanical stimuli. Among the four different polymorphs (α, β, γ, and ϵ), ϵ‐polymorph has better stability and shock/detonics properties. However, preparation of pure ϵ‐polymorph is a challenging task particularly in terms of repeatability and polymorphism. In our research work, pressurized nozzle based solvent/anti‐solvent process (PNSAP) was developed for the preparation of ultrafine ϵ‐CL‐20 explosives with high repeatability, purity, and yield. To get ultrafine particle size, shape, distribution and yield, various process parameters/ variables such as solvent type, anti‐solvent type, dosing rate, stirring rate, ultra‐sonication, and temperature were identified and prioritized using the weighted average method of Analytical Network Process (ANP) techniques. It was observed that ultrafine ϵ‐CL‐20 particle size in the range of 2 to 3 μm can be obtained using this process. The ϵ‐polymorph was confirmed by FT‐IR characterization. The main feature of this PNSAP process is that it is a laboratory scale table‐top pilot plant which is simple, cost‐effective, safe and repeatable for continuous batch production of ultrafine ϵ‐CL‐20 at the rate of 100 grams per hour.     

Study on Ultrasound‐ and Spray‐Assisted Precipitation of CL‐20

Ultrafine hexanitrohexaazaisowurtzitane (CL‐20) samples were prepared by a ultrasound‐ and spray‐assisted precipitation method. Raw CL‐20 and ultrafine CL‐20 samples were characterized by SEM, FT‐IR spectroscopy, XRD, and particle size analysis. The impact sensitivity and thermal stability of two CL‐20 samples were also tested and compared. The results indicate that by this recrystallization process, the mean particle size of CL‐20 is 470 nm, and the particle size distribution was in the range from 400–700 nm. The particle morphology is nearly spheric with a smooth surface. Compared with raw CL‐20, the impact sensitivity of the ultrafine sample is significantely reduced and the drop height (H₅₀) is increased from 12.8 to 37.9 cm. The critical explosion temperature of ultrafine CL‐20 decreased from 235.6 to 229.0 °C, which suggests that the thermal stability of ultrafine CL‐20 is lower than that of raw CL‐20.     

Inertial Separation of Ultrafine Particles Using a Condensational Growth/Virtual Impaction System

ABSTRACT

A system for the separation of ultrafine particles (i.e., particles smaller than 0.1 μm) has been developed and evaluated. Ultrafine particles are first grown by means of supersaturation to a size that can be easily separated in a virtual impactor. Thus, inertial separation of ultrafine particles occurs without subjecting them to a high vacuum. The condensational growth/virtual impaction system has been evaluated using monodisperse 0.05 and 0.1 μm fluorescent PSL particles, as well as polydisperse ultrafine ammonium sulfate and potassium nitrate aerosols. The generated aerosols were first drawn over a pool of warm water (50°C) where they became saturated. Subsequently, the saturated aerosol was drawn through a cooling tube (8°C) where particles grew due to supersaturation to sizes in the range 1.0–4.0 μm. By placing a virtual impactor with a theoretical 50% cutpoint of 1.4 μm downstream of the condenser, ultrafine particles were separated from the majority (i.e., 90%) of the surrounding gas. The sampling flow rate of the virtual impactor was 8 L/min and its minor-to-total flow ratio was 0.1. For these operating conditions, the particle collection efficiency of the virtual impactor averaged to about 0.9 for particle concentrations in the range 7 × 10⁴-5 × 10⁵ particles/cm³. Particle losses through the system were found less than 5%. Increasing the particle concentration to levels in the range 106–107 particles/cm³ resulted in a decrease in the collection efficiency of the virtual impactor to about 50–70%, presumably due to the smaller final droplet size to which the ultrafine particles grew for the available supersaturation.     

Antisolvent crystallization and solid‐state polymerization of bisphenol‐A polycarbonate

Bisphenol‐A polycarbonate (BAPC) was synthesized by solid‐state polymerization (SSP) using a semicrystalline prepolymer crystallized by antisolvent method. The antisolvent crystallization was investigated as a function of antisolvent types using X‐ray diffraction (XRD), different scanning calorimetry (DSC), and scanning electron microscopes (SEM). The results showed antisolvent types had a significant effect on the crystallization of BAPC. Prepolymer induced by acetone as an antisolvent gained a higher crystallinity of 37.0%, more uniform particle size, and mature crystal structure compared with the samples crystallized by methanol and ethanol. Then crystallization of BAPC by acetone was carried out at crystallization temperature in the range of 40–80 °C for 1–5 h. A high crystallinity of 42.0% was acquired with the crystallization conducted at 70 °C for 2 h. Prepolymer with appropriate crystallinity of 37.8% resulted in high‐molecular‐weight polymer of 57,411 via SSP due to the effect of crystallinity and plasticization of residual solvent. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43636.     

Process performances and characteristics of powders produced using supercritical CO2 as solvent and antisolvent

A carbon dioxide (CO₂) soluble compound (cholesterol) was successfully precipitated either by rapid expansion of SCCO₂ solutions (RESS process, acronym for Rapid Expansion of Supercritical Solution), or from methylene chloride solutions by antisolvent precipitation (SAS-process, acronym for Supercritical Antisolvent process). The same fluid was thus used either as a solvent or as an antisolvent to precipitate cholesterol. Performances of RESS and SAS were compared through the analysis of the particle characteristics and production rates. Differences were related to supersaturation and time scale of nucleation/growth involved in both processes. Polydispersity, large size and elongated shape were characteristics of particles produced by SAS, especially when experiments were performed under conditions of total miscibility of CO₂ and organic solvent. Conditions where vapor-liquid equilibrium exists promoted a confinement of the growth that consequently reduced the final particle size. RESS, by comparison, produced smaller and monodispersed particles. Production of small particles is a key advantage for RESS, but lower production rates and yield might be disadvantages. The combination of the two processes offers the opportunity of tunable sizing of powder, switching from a large production of particles ranging from 10 to 100 μm, to a limited production of fine crystals below 10 μm.     

Controlled liquid antisolvent precipitation using a rapid mixing device

Particle formation by the liquid antisolvent (LAS) process involves two steps: mixing of solution–antisolvent streams to generate supersaturation and precipitation (which includes nucleation and growth by coagulation and condensation) of particles. Uniform mixing conditions ensure rapid and uniform supersaturation, making it a precipitation controlled process where the particle size is not further affected by mixing conditions and results in precipitation of ultra-fine particles with narrow particle size distribution (PSD). In this work, we demonstrate that the use of an ultrasonically driven T-shaped mixing device significantly improves mixing of solution and antisolvent streams for precipitation of ultra-fine particles in a continuous operation mode. LAS precipitation of ultra-fine particles of multiple active pharmaceutical ingredients (APIs) such as itraconazole (ITZ), ascorbyl palmitate (ASC), fenofibrate (FNB), griseofulvin (GF), and sulfamethoxazole (SFMZ) in the size range 0.1–30 μm has been carried out from their organic solutions in acetone, dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), and ethanol (EtOH). Classical theory of homogeneous nucleation has been used to analyze the result, which suggests that higher nucleation rate results in finer particle size. Interestingly, experimental determination of degree of supersaturation indicates that higher supersaturation does not necessarily result in higher nucleation rate and nucleation rates can be correlated to solvent polarity.     

The influence of operating conditions on the dense gas precipitation of model proteins

Dense gas techniques provide a suite of clean technology options for the processing of pharmaceuticals. Monodisperse, micron‐sized particles can be produced at mild operating temperatures and with negligible solvent residue. In this study, protein was precipitated from organic solutions using dense carbon dioxide as antisolvent. The gas antisolvent precipitation process (GAS) was used to produce biologically active lysozyme, insulin, and myoglobin powders. The effects of operating temperature, solute concentration and the rate of antisolvent addition on the morphology, size, activity and residual solvent concentration of lysozyme and insulin precipitates have been examined. The powders produced consisted of uniformly sized non‐aggregated spherical particles. Precipitate size was controlled between 0.05 µm and 2.0 µm by changes to the solvent and antisolvent compositions. In general the concentration of residual organic solvent was found to be dependent on the mass of antisolvent used during the washing cycle. Residual concentrations as low as 300 ppm were easily achievable in a single step. © 2000 Society of Chemical Industry     

Effect of Solvent on Nanoparticle Production of β‐Carotene by a Supercritical Antisolvent Process

Production of micro‐ to nano‐sized particles of β‐carotene was investigated by means of solution‐enhanced dispersion by supercritical fluids (SEDS). β‐Carotene was dissolved in dichloromethane (DCM), N,N‐dimethylformamide (DMF), n‐hexane, or ethyl acetate, and supercritical CO₂ served as an antisolvent. The effects of the organic solvents, operating pressure, and temperature were examined. The morphologies of the particles produced by the SEDS were observed by field emission‐scanning electron microscopy and particle sizes were determined by image analysis. Irregularly shaped microparticles were produced in the system with DCM and DMF solution. Plate‐like microparticles were generated by using n‐hexane solution and irregular nanoparticles by ethyl acetate solution. The optimum operating conditions were found to be ethyl acetate as solvent in a defined pressure and temperature range.     

Preparation and Characterization of Nano‐TATB Explosive

Nano‐TATB was prepared by solvent/nonsolvent recrystallization with concentrated sulfuric acid as solvent and water as nonsolvent. Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM) were used to characterize the appearance and the size of the particles. The results revealed that nano‐TATB particles have the shape of spheres or ellipsoids with a size of about 60 nm. Due to their small diameter and high surface energy, the particles tended to agglomerate. By using X‐ray powder diffraction (XRD), broadening of diffraction peaks and decreasing intensity were observed, when the particle sizes decreases to the nanometer size range. The corrected average particle size of nano‐TATB was estimated using the Scherrer equation and the size ranged from 27 nm to 41 nm. Furthermore, the specific surface area and pore diameter of nano‐TATB were determined by BET method. The values were 22 m²/g and 1.7 nm respectively. Thermogravimetric (TG) and Differential Scanning Calorimetric (DSC) curves revealed that thermal decomposition of nano‐TATB occurs in the range of 356.5 °C–376.5 °C and its weight loss takes place at about 230 °C. Furthermore, a slight increase in the weight loss was observed for nano‐TATB in comparison with micro‐TATB.     

超细HNS的形貌控制及性能

采用溶剂-非溶剂重结晶法和晶形控制技术制备超细HNS,并对晶形控制剂的种类和用量、加料方式等因素在重结晶细化过程中对HNS微晶形貌和粒度的影响进行了分析。结果表明,上述几种因素对超细HNS的形貌、粒径及团聚的影响较大。对于0.40g的HNS原料,采用3mL质量分数0.5%的淀粉分解产物(DT)作为晶形控制剂,针管滴加药液,所得晶体大多为椭球形及球形小颗粒,部分呈规则块状,流散性好,粒径分布在100~400nm且无团聚;采用1.8mL质量分数1%的聚氧乙烯醚类化合物(PT)作为晶形控制剂,针管滴加药液,所得晶体绝大多数为球形小颗粒,粒径分布范围较窄,最小粒径可达50nm。细化后HNS的耐热均匀性略有提高,并且能够被标准黑药柱点燃,其50%发火高度约为12cm。