Supercritical Antisolvent Method Research Articles

Micro and nanosizing of Tamsulosin drug via supercritical CO2 antisolvent (SAS) process

Supercritical anti-solvent (SAS) method is a solvent-free approach where supercritical carbon dioxide (SC-CO2) is used as anti-solvent and one can control the output particle size without disturbing the nature of the particles. The primary objective of this study is to develop SAS method for the production of Tamsulosin (TML) nanoparticles and investigate the parameters affecting the resultant particle size. In order to optimize the production of nano-sized particles, response surface methodology (RSM) based on Box-Behnken design (BBD (was used. Using dynamic light scattering (DLS) and scanning electron microscopy (SEM) analyses, morphologies and mean diameter ranges were examined. To look into how the SAS process affects TML's chemical and physical characteristics, Fourier-transform infrared spectroscopy (FT–IR), X-ray diffraction analysis (XRD) and differential scanning calorimetry (DSC) were further performed. The acquired results demonstrated that the pressure imposes the largest impact on the TML particle production, with the particle size exhibiting an inverse correlation to the pressure. Observations further indicated an increase in particle size with increasing the temperature from 35 to 50 °C. By increasing the flow rate of the drug solution, the average particle size exhibited an initial decrease followed by an increasing trend. Results of the optimization of the SAS process showed that at a pressure, temperature, and injection rate of 25 MPa, 41.3 °C, and 2.9 mL/min, respectively, the TML particles shrink to an average size of 600 nm.

Supercritical antisolvent method for recrystallization of HMX

Supercritical antisolvent method for recrystallization of HMX

Supercritical fluid-assisted fabrication of Pt-modified cerium oxide nanozyme based on polymer nanoreactors for peroxidase-like and glucose detection characteristics

To address the key problems of natural proteases in terms of stability, transportation and storage, this work demonstrates the preparation of a Pt/CeO2 precursor based nanozymes for glucose detection using a user-friendly supercritical CO2 "nanoreactor" technique. The optimum parameters in this supercritical fluid (SCF) technology were discussed by using the full-factor design. Through the analysis of the valence states of Pt/CeO2 obtained by the one-step calcination of the precursor, the catalytic mechanism was explored by increasing the Pt0 content at the main catalytic active site. Following Michaelis–Menten theory, the detection limit of glucose sensor is around 11.9 μM in a linear range of 100 μM to 500 μM, better than pure CeO2. Thus, this work demonstrated a rapid, green, and easy approach with controlled preparation of Pt/CeO2 based on the supercritical antisolvent method, providing great potential for the preparation of metal oxide-based nanozyme and rapid colorimetric detection of glucose.

Micronization of Levofloxacin Hydrochloride by the Supercritical Antisolvent Precipitation Method from Single-Phase and Two-Phase CO2–Acetone Mixtures

Micronization of Levofloxacin Hydrochloride by the Supercritical Antisolvent Precipitation Method from Single-Phase and Two-Phase CO2–Acetone Mixtures

Development of highly stable ICG-polymeric nanoparticles with ultra-high entrapment efficiency using supercritical antisolvent (SAS)-combined solution casting process

Indocyanine green (ICG), a water-soluble near-infrared (NIR) photosensitizer, has been enormously regarded in tumor diagnosis and phototherapy. Although tremendous progress in establishing the nanocarrier-based delivery systems has been explored, several limitations of low ICG encapsulation and sophisticated fabrication process remain significant challenges in producing nanoplatforms, limiting the theranostic outcomes of ICG. According to the unique advantages of the supercritical antisolvent (SAS) process and solution casting method, a novel combination approach to obtain the ICG-loaded nanoparticles (ICG-PLO NPs) is demonstrated, in which SAS assisted-ICG nanoparticles (ICG NPs) are coated with polypeptide poly-l-ornithine (PLO) using solution casting approach. This unique nanoplatform with ultra-high drug encapsulation efficiency remarkably improved the aqueous and photothermal stability of ICG. Notably, the coating of PLO could improve the internalization level in cells and anticancer effect in vivo, comprehensively augmenting the cancer phototherapy effect of ICG. Together, the findings of novel particle formation by integrated strategy would certainly broaden the applications of supercritical fluid (SCF) technology, potentiating the design of nano-formulations of ICG for clinical translation.

Advanced High-Loaded Ni–Cu Catalysts in Transfer Hydrogenation of Anisole: Unexpected Effect of Cu Addition

Binary Ni–Cu heterogeneous catalysts are known to demonstrate excellent activity in conventional hydrogenation of phenolic compounds, and Cu addition facilitates hydrodeoxygenation (HDO). In this study, we aimed to show the effect of Cu on the specific catalytic activity and selectivity of Ni–Cu catalysts in transfer hydrogenation, in which 2-PrOH was used as a solvent and an H donor. Catalytic transformations of anisole were studied in sub- and supercritical alcohol at 150 and 250 °C. The catalysts were prepared using an environmentally friendly supercritical antisolvent coprecipitation method, which makes it possible to obtain well-dispersed particles (less than 7 nm) at high metal loading (up to 50 wt.%). When copper is added, deactivation of the catalyst in transformations of anisole, including HDO, is observed. The experimental data and the appropriate kinetic analysis demonstrate that there is a decrease in the rate of anisole conversion accompanied by an increase in the concentration of acetone formed during the dehydrogenation of 2-PrOH.

Solubility measurement of the fludrocortisone acetate in supercritical carbon dioxide: Experimental and modeling assessments

Solubility of pharmaceutical compounds in the supercritical carbon dioxide (sc-CO2) is an essential parameter in the development of the pharmaceutical industry. In this work, the solubility of fludrocortisone acetate was measured in sc-CO2 at the pressure and temperature ranges of 120 − 300 bar and 308–338 K, respectively. Moreover, the experimental solubility data were correlated using several empirical models (Chrastil, Mendez-Santiago & Teja, Bartle, and Kumar & Johnston), a non-cubic equation of state (PC-SAFT), and a UNIQUAC model. The mole fraction of the drug in sc-CO2 was varied in the range of 0.211 × 10-6 to 0.653 × 10-5. The solubility shows a complete dependence on operating pressure and temperature. Furthermore, MST and PC-SAFT models exhibited the highest accuracy with respective Radj values of 0.994 and 0.993. Regarding the poor solubility of FLU in sc-CO2, a supercritical anti-solvent method can be an appropriate choice to produce fine particles of this drug.

Preparation of astragaloside IV (AS-IV) nanoparticles via SAS process for anticancer efficacy: Optimization based on Box-Behnken Design

Despite significant advances in drug formulation, the clinical application of most active pharmaceutical ingredients from traditional Chinese herbs remained a significant challenge due to their poor solubility. To address this crucial issue, astragaloside-IV (AS-IV) was selected as a model drug to prepare nanoparticles with a large specific surface area via a constant, steady, and well-organized supercritical antisolvent (SAS) method. Initially, the optimal range of nanoparticle nucleation was determined by a single-factor investigation under altered critical conditions. Under the optimized conditions obtained from the Box-Behnken Design model analysis (AS-IV solution flow rate (F): 0.85 mL/min, Temperature (T): 42 ℃, Pressure (P): 120 bar), the SAS process resulted in nanospheres with smooth surface and narrow particle size distribution. After the SAS process treatment, AS-IV with altered physical states presented improved solubility and enhanced in vitro antiproliferative effects compared to untreated AS-IV, illustrating the potential application of the SAS method in promoting the bioavailability of low water-soluble drugs.

Extraction of diterpenes from spent coffee grounds and encapsulation into polyvinylpyrrolidone particles using supercritical carbon dioxide

ABSTRACT In this study, supercritical carbon dioxide (SC-CO2) was used to extract diterpenes from spent coffee grounds (SCGs) and it is followed by the encapsulation of SCG extract into polyvinylpyrrolidone particles using a supercritical antisolvent crystallization method. In the extraction process using SC-CO2, the effects of three independent variables – temperature (40‒80°C), pressure (10‒30 MPa), and the ratio of ethanol as a modifier (0%‒10% v/v), on dependent variables: extraction yield and total diterpene content – were investigated using the response surface methodology and Box – Behnken design. The optimal conditions for the extraction yield and total diterpene content were predicted to be 40°C/30 MPa/10% v/v of ethanol and 80°C/25 MPa/6% v/v of ethanol, respectively. Notably, the predicted maximum total diterpene content was 15 times the amount obtained by the Soxhlet method using n-hexane, thereby confirming the selectivity of ethanol-modified SC-CO2 toward diterpenes. Subsequently, based on the supercritical antisolvent crystallization process, the SCG extract was successfully encapsulated into polyvinylpyrrolidone particles with an average particle size of 140 nm, and the water dispersibility of the SCG extract was enhanced by this encapsulation process. The encapsulation of SCG extract with water-soluble polymers enables the further use of SCG extract in food, cosmetic, and pharmaceutical industries.

Micronization of Curcuma xanthorrhiza Extract with Addition of PVP Using Supercritical CO2 as Anti-solvent

Curcuma xanthorrhiza Roxb, known as Temulawak or Javanese ginger, is a plant species. Its rhizomes are used as a medicinal herb. It contains curcumin as an active compound and ethereal oils mainly consisted of sesquiterpenes. In this work, Curcuma xanthorrhiza Roxb ethanolic extract was micronized with an addition of PVP using supercritical antisolvent (SAS) method. The ethanolic extract was obtained from dried Curcuma xanthorrhiza Roxb using soxhletation. For the micronization, the extracted compound solvent was a mixture of acetone and ethanol (90:10 (v/v)), while the supercritical CO2 was used as an antisolvent. The effect of operating conditions on the particle size and morphology was evaluated. Through this method, spherical Curcuma xanthorrhiza/PVP particles with mean diameter ranging from 191 ± 70 nm to 178 ± 57 nm were successfully formed. The particle size not significantly decreased as the pressure increased from 8 12 MPa. The addition of PVP is very effective to reduce the particle size, increase the solubility, and enhance the bioavailability of Curcuma xanthorrhiza extract. This work has the potential to improve the use of Curcuma xanthorrhiza in pharmaceutical and nutraceutical applications.

Size-Controlled Synthesis of CuO Nanoparticles by the Supercritical Antisolvent Method in SBA-15

Herein, we describe a facile method to control the size and dispersion of CuO nanoparticles (NPs) in SBA-15 by the supercritical antisolvent (SAS) method during the depressurization process of supercritical fluid deposition (SCFD), describing the mass transfer between supercritical carbon dioxide (scCO2) and a cosolvent. On reducing the concentration of the cupric nitrate precursor, the size of CuO NPs was decreased from 3.5 ± 1.0 to 1.0 ± 0.4 nm (Cu loading 14.2–12.1 wt %) under the depressurized rate of ∼20 MPa/min. Based on the size distribution and nucleation theory, the nucleation rate of the precursor could reach 1025 cm–3·s–1, and the calculated interface energy of cupric nitrate was less than 0.1 J/m2, indicating that scCO2 as an antisolvent caused the heterogeneous nucleation of the precursor on the surface of SBA-15 channels. Hence, the nucleation rate and growth of cupric nitrate were regulated under a given scCO2 depressurized rate, and then the CuO NPs’ size distribution and Cu loading were controlled subsequent to calcination.

Advanced green approaches for the synthesis of NiCu-containing catalysts for the hydrodeoxygenation of anisole

NiCu-containing catalysts stabilized by SiO2 with a different metals ratio are prepared via the «green» supercritical antisolvent (SAS) precipitation method. Obtained catalysts are characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and CO adsorption. The addition of water and a silica sol into precursor solution allows us to obtain highly loaded (70 wt. % of metals) dispersed metal catalysts with a Ni1-xCux solid solution structure without phase separation into individual metals. These heterogeneous catalysts are used for hydrodeoxygenation of anisole – a model compound of pyrolysis liquid. The main product of the hydrodeoxygenation process over prepared catalysts was cyclohexane.

Effect of solvent selection and nozzle geometry on Curcuma mangga micronization process using supercritical antisolvent: Experiment and CFD simulation

In this study, ethanolic extracts of Curcuma mangga (C. mangga) were micronized using the supercritical antisolvent (SAS) method. Acetone, ethyl acetate, and dichloromethane were used as solvents to study the effects of solvent selection on the obtained particles. Supercritical carbon dioxide (CO2) was used as the antisolvent. The effects of nozzle geometry (cross nozzle and T-nozzle) on particle size and morphology were also evaluated. Microparticles and submicron particles were successfully produced with particle sizes ranging from 0.202 ± 0.05 μm to 1.653 ± 0.89 μm. Of the three solvents, ethyl acetate produced smaller particle sizes with a narrow particle size distribution. For all the types of solvents used, micronized particles prepared with the cross-nozzle had smaller average particle sizes than with the T-nozzle. The smallest particles of mean size 0.202 ± 0.05 μm were achieved at 16 MPa and 313 K using ethyl acetate as the solvent and a cross-nozzle. Computational fluid dynamics simulations were successfully performed on the internal flow to study the turbulent flow and volume fraction inside the nozzle. The results of this are expected to help improve the applications of the active ingredients of C. mangga rhizomes in the pharmaceutical industry.

Optimization of process parameters for preparation of polystyrene PM2.5 particles by supercritical antisolvent method using BBD-RSM

The objective of this study is to optimize the process parameters for preparing polystyrene (PS) PM2.5 particles by supercritical antisolvent (SAS) method. Toluene was selected as the solvent and supercritical carbon dioxide (SC-CO2) was used as the antisolvent. The Box–Behnken design-response surface method was applied to investigate the effect of crystallizer pressure, PS massic concentration, flow ratio of CO2/solution and crystallizer temperature on the size and the distribution of PS particles, systematically. It is found that crystallizer temperature is the most significant variable on the size and the distribution of PS particles, followed by flow ratio of CO2/solution and PS massic concentration, and crystallizer pressure is the slightest significant factor. The particle size increases with the increase of crystallizer temperature. The optimum conditions are obtained as crystallizer pressure 9.8 MPa, PS massic concentration 1.6 wt%, flow ratio of CO2/solution 140 g/g and crystallizer temperature 309 K. Under these conditions, the PS particle with the size of 2.78 μm and a narrow size distribution has been prepared, meeting PM2.5 standard aerosols. The results suggest that it is feasible to produce PM2.5 standard aerosols by SAS.

Preparation of Berberin Proliposomes by Film Deposition on Carrier Surface Method

This study aims to formulate berberin (BBR) proliposomes by film-deposition on carrier surface to increase BBR’s solubility and permeability through biological membranes. Proliposomes were hydrated in water to form BBR liposomes for determining the size and distribution of the vesicles. Differential thermal analysis was used to evaluate the BBR proliposomes. The study results show that berberin proliposomes prepared with hydrogenated soy phosphatidylcholine: cholesterol: berberin with a molar ratio of 9:1:6 using sorbitol as carrier with a weight ratio to lipid of 10:1. The obtained BBR proliposomes in the form of a dry yellowish powder were hydrated in water to form BBR liposomes with an average diameter of about 8.41μm. The results of the differential thermal analysis show that BBR was dispersed in molecular form into proliposomes. 
 Keywords:
 Berberin, proliposomes, sorbitol, film-deposition on the carrier method.
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Investigation of precipitation selectivity and particle size concentration dependences in supercritical antisolvent method via online supercritical fluid chromatography

Supercritical antisolvent (SAS) precipitation technique, although being versatile and ecologically friendly, suffers from the lack of convenient methods for necessary thermodynamic parameters measurement. Recently we have proposed a method for solubility measurement in binary fluids based on an online hyphenation of supercritical antisolvent method and supercritical fluid chromatography (SAS-SFC). In this paper, we demonstrate the applicability of this method to the investigation of both selective precipitation from solution and particle size tuning in SAS using lower dicarboxylic acids as model objects. Measured solubility values adequately reflect selective crystallization from solution. SAS precipitation was observed only for those components, which concentration was above solubility in CO2-solvent mixture as predicted by SAS-SFC method. Also, concentration dependences of particle size plotted in supersaturation coordinates instead of direct concentration in initial solution give additional insight into crystallization behaviour in SAS.

Fabrication of Supercritical Antisolvent (SAS) Process-Assisted Fisetin-Encapsulated Poly (Vinyl Pyrrolidone) (PVP) Nanocomposites for Improved Anticancer Therapy.

Due to its hydrophobicity, fisetin (FIS) often suffers from several limitations in terms of its applicability during the fabrication of pharmaceutical formulations. To overcome this intrinsic limitation of hydrophobicity, we demonstrate here the generation of poly (vinyl pyrrolidone) (PVP)-encapsulated FIS nanoparticles (FIS-PVP NPs) utilizing a supercritical antisolvent (SAS) method to enhance its aqueous solubility and substantial therapeutic effects. In this context, the effects of various processing and formulation parameters, including the solvent/antisolvent ratio, drug/polymer (FIS/PVP) mass ratio, and solution flow rate, on the eventual particle size as well as on distribution were investigated using a 23 factorial experimental design. Notably, the FIS/PVP mass ratio significantly affected the morphological attributes of the resultant particles. Initially, the designed constructs were characterized systematically using various techniques (e.g., chemical functionalities were examined with Fourier-transform infrared (FTIR) spectroscopy, and physical states were examined with X-ray diffraction analysis (XRD) and differential scanning calorimetry (DSC) techniques). In addition, drug release as well as cytotoxicity evaluations in vitro indicated that the nanosized polymer-coated particles showed augmented performance efficiency compared to the free drug, which was attributable to the improvement in the dissolution rate of the FIS-PVP NPs due to their small size, facilitating a higher surface area over the raw form of FIS. Our findings show that the designed SAS process-assisted nanoconstructs with augmented bioavailability, have great potential for applications in pharmaceutics.

An outline on curcumin: Its pro-liposome and liposome formulations

Curcumin (Cur) is broadly accepted for its useful functions. Cur has low water solubility therefore its application in drug delivery became a challenge for researchers. To overcome the absorption, bioavailability and overall biochemical/structural degradation we may develop pro-liposomes and liposomes of Cur. The proliposomes generally administrated by orally, topically and parentally and mainly used in cosmetic and hair technologies, diagnostic purpose, sustained release formulations and as good carriers in gene delivery. This review highlights the speculative approach and some new advancement for the preparation of pro-liposomes in general. Various methods to formulate pro-liposomes (Film-deposition carrier method, Spray drying method, Fluidized-bed method, Supercritical anti-solvent method), evaluation parameters (Hydration study, Zeta potential, Flow property) there of and applications of pro-liposome are highlighted. This may help for further preparation and evaluation of Cur. based formulations. Additionally different features of curcumin related to its pharmacological profile and mechanism of protection in various ailments have been reported.

Response surface methodology to optimize the preparation of tosufloxacin tosylate/hydroxypropyl-β-cyclodextrin inclusion complex by supercritical antisolvent process

Response surface methodology was designed to optimize the process parameters for the preparation of the tosufloxacin tosylate/hydroxypropyl-β-cyclodextrin inclusion complex by supercritical antisolvent method (SAS). The optimum inclusion conditions were temperature 45 °C, pressure 12 MPa, molar ratio 1:1, and mixed solvent 20% DCM, in which case the inclusion efficiency was 15.18%. Three-dimensional response plots revealed that molar ratios and mixed solvents have a more pronounced effect on inclusion efficiency than temperature and pressure. Characterization results of SEM, EDX, PXRD and FT-IR confirmed that the inclusion complex was successfully prepared, and the inclusion sites of all inclusion complexes were located on the phenyl ring A, pyrrolidine and naphthyridine ring protons. The dissolution of the inclusion complex in the pH 6.8 buffer solution was up to 68.14%, indicating that the inclusion complex prepared by the SAS process could significantly improve the dissolution of tosufloxacin tosylate.

Mesoporous aerogel-like Al-Si oxides obtained via supercritical antisolvent precipitation of alumina and silica sols

A method of alumina and silica sols precipitation in supercritical CO2 has been developed for the first time to prepare alumina and silica doped alumina. The silicon content of samples is varied within the range from 0 to 30 mol. %. The approach suggested can be considered as a development of supercritical antisolvent (SAS) method that is widely used to prepare powders from solutions but not sols. The alumina and silicon-doped alumina obtained are shown to be mesoporous materials with narrow size distribution in the range of 3–5 nm. The high-temperature treatment of the sample containing 10 mol. % of Si results in the formation of γ-Al2O3 phase followed by its transition into the δ-Al2O3 phase at 1200 °C without α-Al2O3 phase formation. It is demonstrated that the gradual introduction of silica into the alumina allows one to fine-tune the strength and amount of acid sites existing in oxides.