Supercritical Antisolvent Research Articles

Enhanced drug release through nitrendipine/hydroxypropyl methylcellulose solid dispersion via supercritical antisolvent technique

The poor water solubility of nitrendipine (NT) results in low oral bioavailability, which hinders its practical application. Hydroxypropyl methylcellulose (HPMC) is a prominent drug carrier that has been applied in the biomedical field due to its significant characteristics, such as large surface area, biocompatibility and biodegradability. In this study, an efficient drug delivery system based on the preparation of NT/HPMC solid dispersion using supercritical antisolvent (SAS) technology was proposed. The effect of different operating parameters such as solvent, host guest ratio, concentration, temperature, and pressure on NT/HPMC was optimized to obtain dispersed particles with maximum solubility. The formed solid dispersion presents non-static spherical particles with a high surface area and small particle size. Importantly, in vitro drug release studies have demonstrated that the dissolution and solubility of NT in solid dispersion are significantly enhanced compared to pure drug. In vitro bioactivity experiments showed that the NT/HPMC solid dispersion has good biocompatibility and antibacterial performance. Thus, this study indicates that solid dispersion prepared using SAS technology are considered a promising drug delivery system.

Micronization of ciprofloxacin by the Supercritical Antisolvent (SAS) Technique

Ciprofloxacin is a broad-spectrum antibiotic that is proposed for pulmonary administration. In this work micronization of ciprofloxacin was performed by the Supercritical Antisolvent Technique (SAS) using ciprofloxacin base (CIP) in ethanol/acetic acid and ciprofloxacin hydrochloride salt (CIP·HCl) in methanol at 40–60 ºC and 100–150 bar. Yields ranged from 40 % to 90 %. CIP precipitated incorporating acetate whilst CIP·HCl precipitated as the AH1 anhydrous form. CIP and CIP·HCl particles exhibited an acicular morphology (0.2–0.9 μm wide × 1–4 μm long). Micronization adding lactose, PVP K-10 and K-30 modified the precipitate morphology. CIP·HCl:lactose and CIP·HCl:PVP K-30 at a 4:1 drug:excipient mass ratio precipitated like flakes. CIP·HCl:PVP K-10 precipitated as submicron globular particles suitable for oral formulation. Increasing the PVP content, the morphology changed to sheets and flakes, which could be used for pulmonary administration. The antibacterial activity of the samples for Staphylococcus epidermidis was confirmed.

Controlling particle size of levan in powder form with different technologies

Levan is a fructose polysaccharide with multiple applications in different fields, but its obtaining in powdered form with a narrow particle size distribution is a complicated task. Two techniques, electrospraying and supercritical antisolvent (SAS) precipitation, were used to process levan that was first obtained enzymatically. The SAS process was able to micronize the polymer (at experimental conditions far above the mixture critical point of the solvent-antisolvent system) to obtain spherical particles between 0.30 and 0.50 μm with a proper particle size distribution. In this case, the Peng-Robinson equation of state was used to theoretically determine the mixture critical point. Bigger and elongated particles were obtained with electrospraying (0.60 μm). According to solution properties, mainly rheology, solubility and conductivity, the best solvent for levan electrospraying, in order to avoid problems of solvent evaporation and jet formation, was a mixture of water and ethanol with a polymer concentration of 50 mg·cm−3. Indeed, that solution has a viscous behavior (according to the oscillatory analysis), a low degree of pseudo-plasticity (based on the shear flow analysis), and the highest value of conductivity. Therefore, the particle size distribution of levan in powdered form can be tuned depending on the technique used.

CeO2-CuO composites prepared via supercritical antisolvent precipitation for photocatalytic hydrogen production from lactic acid aqueous solution

The global increase in energy demand requires a continuous search for renewable and clean alternative resources to fossil fuels. Hydrogen is emerging as a promising energy carrier for the future; its production via photocatalysis, driven by sunlight, can directly convert solar energy into a usable or storable energy resource. However, water splitting requires sacrificial agents or electron donors/hole scavengers, such as short-chain organic acids. This research explores the use of lactic acid as a source for photocatalytic hydrogen production, offering valuable alternatives for wastewater management and renewable energy production. This study employed the innovative supercritical antisolvent (SAS) technique to micronize the precursors of both the active phase (CeO2) and co-catalyst (CuO), ensuring rapid and complete solvent removal and size reduction of photocatalyst precursors. The prepared samples were characterized by field emission scanning electron microscopy (FESEM), Fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS) analysis, Brunauer-Emmett-Teller (BET) analysis and thermogravimetric analysis (TGA). This study has shown that the micronization process resulted in a notable improvement in CeO2 photocatalytic activity, attributed to the reduction of the dimensions of the powders. Hydrogen production was equal to 3989 μmol L−1 for the SAS-produced photocatalyst while using a commercial CeO2 sample resulted in H2 production of 2519 μmol L−1. The enhanced photoactivity of CeO2-CuO composites was found to be related to the presence of CuO. The optimal CuO amount was equal to 0.5 wt%, determining a hydrogen production of 9313 μmol L−1 after 4 h of UV irradiation time. A photocatalytic test carried out with deuterated water (D2O) instead of distilled H2O demonstrated that hydrogen was preferentially produced from water splitting reaction, whereas lactic acid acted as a sacrificial agent being oxidized from positive holes photogenerated in the valence band of CuO.

Biosensing of Cysteine through the Induction of Oxygen Vacancies in a Cu/Zr Heterostructure Prepared by Supercritical Antisolvent Technique.

There has been a growing emphasis on facile preparation of binary heterogeneous composite materials. Leveraging the eco-friendly efficiency of supercritical CO2 technology, we achieved precise control over the influencing factors of mass transfer, enabling the accurate modulation of the resulting product morphology and properties. In the current study, CuxO/ZrOy composite materials were prepared using this technology and calcined to obtain electrode materials for the detection of cysteine (Cys). Essential comprehensive characterization techniques were employed to elucidate the heterojunction. The resulting electrode demonstrated a linear response to Cys within a concentration range of 0.5 nM to 1 μM, featuring a high sensitivity of 1035 μA·cm-2·μM-1 and a low detection limit of 97.3 nM. Thus, establishing a novel avenue for nonenzyme-based electrochemical sensors tailored for biologically active Cys detection through the implementation of a heterogeneous structure.

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.

PVP/aprepitant microcapsules produced by supercritical antisolvent process

The supercritical antisolvent (SAS) process was a green alternative to improve the low bioavailability of insoluble drugs. However, it is difficult for SAS process to industrialize with limited production capacity. A coaxial annular nozzle was used to prepare the microcapsules of aprepitant (APR) and polyvinylpyrrolidone (PVP) by SAS with N, N-Dimethylformamide (DMF) as solvent. Meanwhile, the effects of polymer/drug ratio, operating pressure, operating temperature and overall concentration on particles morphology, mean particle diameter and size distribution were analyzed. Microcapsules with mean diameters ranging from 2.04 μm and 9.84 μm were successfully produced. The morphology, particle size, thermal behavior, crystallinity, drug content, drug dissolution and residual amount of DMF of samples were analyzed. The results revealed that the APR drug dissolution of the microcapsules by SAS process was faster than the unprocessed APR. Furthermore, the drug powder collected every hour is in the kilogram level, verifying the possibility to scale up the production of pharmaceuticals employing the SAS process from an industrial point of view.

Acetazolamide encapsulation in elastin like recombinamers using a supercritical antisolvent (SAS) process for glaucoma treatment

Glaucoma, the second most common cause of blindness worldwide, requires the development of new and effective treatments. This study introduces a novel controlled-release system utilizing elastin-like recombinamers (ELR) and the Supercritical Antisolvent (SAS) technique with supercritical CO2. Acetazolamide (AZM), a class IV drug with limited solubility and permeability, is successfully encapsulated in an amphiphilic ELR at three different ELR:AZM ratios, yielding up to 62 %. Scanning electron microscopy (SEM) reveals spherical microparticles that disintegrate into monodisperse nanoparticles measuring approximately 42 nm under physiological conditions. The nanoparticles, as observed via Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM), do not exhibit aggregates, a fact confirmed by the zeta potential displaying a value of –33 mV over a period of 30 days. Transcorneal permeation tests demonstrate a 10 % higher permeation level compared to the control solution, which increases to 30 % after 2 h. Ocular irritation tests demonstrate no adverse effects or damage. Intraocular pressure (IOP) tests conducted on hypertensive rabbits indicate greater effectiveness for all three analyzed formulations, suggesting enhanced drug bioavailability during treatment. Consequently, the combination of recombinant biopolymers and high-pressure techniques represents a promising approach for advancing glaucoma therapy, emphasizing its potential clinical significance.

Preparation of indapamide-HP-β-CD and indapamide-PVP nanoparticles by supercritical antisolvent technology: Experimental and DPD simulations

The poor aqueous solubility of indapamide (INP) limits its applicability in various biomedical applications. To overcome this issue, nanosized INP particles (INP-HP-β-CD NPs and INP-PVP-K30 NPs) were fabricated using the supercritical antisolvent (SAS) approach to improve the bioavailability of INP. The process, formula, and supercritical antisolvent process were optimized using single-factor and orthogonal methods. The tiny INP-HP-β-CD NPs with a particle size of 142.5 nm and INP-PVP-K30 NPs with a particle size of 150.4 nm were obtained under optimum conditions. Further analysis and characterization, such as SEM, FTIR, XRD, DSC, 1H NMR, and dissipative particle dynamics (DPD) simulations, were carried out to verify the formation mechanism of the INP complex nanoparticles. The altered physical state of INP from crystalline to amorphous loaded onto the polymer resulted in a significant improvement in the solubility and dissolution rate and high biocompatibility with cells compared to raw INP. Therefore, we propose that INP nanoparticles processed by a supercritical antisolvent process can be used as an advanced drug delivery system, especially for insoluble drugs.

Curcumin/Carrier Coprecipitation by Supercritical Antisolvent Route.

In this work, polyvinylpyrrolidone (PVP)- and β-cyclodextrin (β-CD)-based composite powders containing curcumin (CURC) were obtained through the supercritical antisolvent (SAS) technique. Pressure, total concentration of CURC/carrier in dimethylsulfoxide, and CURC/carrier ratio effects on the morphology and size of the precipitated powders were investigated. Using PVP as the carrier, spherical particles with a mean diameter of 1.72 μm were obtained at 12.0 MPa, 20 mg/mL, and a CURC/PVP molar ratio equal to 1/2 mol/mol; using β-CD as the carrier, the optimal operating conditions were 9.0 MPa and 200 mg/mL; well-defined micrometric particles with mean diameters equal to 2.98 and 3.69 μm were obtained at molar ratios of 1/2 and 1/1 mol/mol, respectively. FT-IR spectra of CURC/ β-CD inclusion complexes and coprecipitated CURC/PVP powders revealed the presence of some peaks of the active compounds. The stoichiometry of the complexes evaluated through the Job method revealed that β-CD formed inclusion complexes with CURC at a molar ratio equal to 1/1. Dissolution profiles revealed that in comparison with the curve of the pure ingredient, the SAS-processed powders obtained using both PVP and β-CD have an improved release rate.

Supercritical Antisolvent Precipitation of Corticosteroids/β-Cyclodextrin Inclusion Complexes.

In this study, corticosteroid-β-cyclodextrin (β-CD) inclusion complexes were prepared by using supercritical antisolvent (SAS) precipitation to enhance the dissolution rate of dexamethasone (DEX) and prednisolone (PRED), which are poorly water soluble drugs. The processing of the active principles in the absence of a carrier led to their almost complete extraction (the small amount of obtained material precipitates in the form of crystals). The coprecipitation of the ingredients in the presence of β-CD was investigated at different concentrations, pressures, and molar ratios. For both the corticosteroids, the optimized operating conditions were 40 °C, 120 bar, an equimolar ratio, and a concentration in DMSO of 20 mg/mL; these conditions led to the attainment of microparticles with mean diameters equal to 0.197 ± 0.180 μm and 0.131 ± 0.070 μm in the case of DEX and PRED, respectively. Job's method confirmed the formation of inclusion complexes with a 1/1 mol/mol ratio. Compared to the pure ingredients, the obtained powders have an improved release rate, which is about three times faster in both cases. The release curves obtained under the best operating conditions were fitted using different models. The best fitting was obtained using the Weibull model, whose parameters are compatible with a combined release mechanism involving Fickian diffusion and controlled release.

Photocatalytic Degradation of Ceftriaxone Using TiO2 Coupled with ZnO Micronized by Supercritical Antisolvent Route.

Heterogeneous photocatalysis is a promising technique for removing pollutants from water. In this work, supercritical antisolvent (SAS)-micronized ZnO (ZnOSAS) is coupled with commercial anatase TiO2 (PC50) to study the photocatalytic degradation of ceftriaxone under UV and visible light. Diffuse ultraviolet-visible reflectance (UV-vis DRS) measurement revealed that the presence of ZnO leads to a slight absorption in the visible region. Wide-angle X-ray diffraction (WAXD) analysis showed the presence of both ZnO wurtzite and TiO2 anatase crystalline phases in the composite. Photocatalytic tests proved that the activity of the ZnOSAS/PC50 composite is higher than that of commercial ZnO, SAS-micronized ZnO, and PC50, allowing complete ceftriaxone degradation under UV light after only 2 min of irradiation time. In contrast, about 90% of ceftriaxone degradation is achieved after 180 min of visible-light irradiation. The photocatalytic results for an experiment carried out in the presence of probe scavenger molecules for reactive oxygen species show that hydroxyl radicals and positive holes are both reactive species involved in the ceftriaxone photocatalytic degradation mechanism. Finally, reuse cycles of the ZnOsas/PC50 composite are performed, demonstrating the stability and recyclability of the photocatalyst.

Supercritical fluid-assisted fabrication of CuxOSAS-based electrochemical sensor for cysteine detection with enhanced sensitivity and reduced oxidation potential

This work demonstrates a rapid and effective strategy to make a cysteine detection system with higher sensitivity and lower detection limit using an eco-friendly supercritical antisolvent (SAS) technology. Copper salt particles were prepared via SAS and transformed into copper(I/II) oxide (CuxOSAS) upon calcination at 400℃. The resulting calcinated product exhibited a significantly reduced particle size and the presence of mixed valence states. The fabricated CuxOSAS cysteine detection system demonstrated excellent performance, with a cyclic voltammetry (CV) curve displaying a low oxidative overpotential (∼0.1 V vs. Ag/AgCl). The linear detection range was 0.001 μM to 0.25 μM and 0.25 μM to 1000 μM, respectively, with corresponding sensitivity of 2447.1 μA·cm−2·μM−1 and 0.3714 μA·cm−2·μM−1, respectively. In conclusion, the SAS-prepared CuxOSAS hold great prospective for electro-sensing and biomolecular catalysis applications.

Cocrystal screening of anticancer drug p-toluenesulfonamide and preparation by supercritical antisolvent process

p-Toluenesulfonamide (PTS) is a new anticancer drug in development. Its poor dissolution behavior complicates the design and development of the formulation process. The present study aimed to improve the dissolution profile of PTS by using a cocrystal engineering approach. Cocrystal screening of PTS with commonly used coformers was investigated, including 4,4′-bipyridine, nicotinamide, isonicotinamide, and sulfacetamide. According to the results of PXRD, FTIR, DSC, and elemental analyzer, a cocrystal of PTS with coformer 4,4′-bipyridine in a stoichiometric ratio of 2:1 was first disclosed. The single crystal of this cocrystal was then prepared, and the crystallographic data were identified and reported. In addition, an intensified crystallization technique, the supercritical antisolvent (SAS) process, was applied to produce this cocrystal using CO2 as the antisolvent. The effect of SAS process parameters was studied, including the operating temperature, operating pressure, solution flow rate, and nozzle diameter. Optimized SAS conditions were proposed for cocrystal preparation, yielding a total powder recovery of approximately 70% and a purity level of up to 90%. Furthermore, according to the results of the dissolution rate study, the dissolution rate of SAS-produced cocrystal was enhanced considerably about 375 times compared to the physical mixture.

Synthesis of highly stable encapsulated astaxanthin/β-cyclodextrin microparticles using supercritical CO2 as an antisolvent

Although astaxanthin has promising physiological functions, its practical applications are limited by poor stability. Herein, astaxanthin was encapsulated in β-cyclodextrin (βCD) using CO2 as a supercritical antisolvent (SAS). The effects of process conditions, including temperature (313–333 K), pressure (12–18 MPa), solution concentration (3–5 wt%), solution flow rate (0.8–1.2 mL min−1), and astaxanthin-to-βCD mole ratio (1:50, 1:25, or 1:10), on the encapsulation efficiency, particle morphology, and residual solvent content were investigated. Astaxanthin–βCD complex spheres with an average diameter of 0.44 ± 0.08 µm were produced at 313 K and 15 MPa with a solution concentration and flow rate of 5 wt%, and 1.0 mL min−1, respectively. Under these optimal conditions, almost complete encapsulation (99.6% encapsulation efficiency) and residual organic solvent removal (0.22 ppm in the complex) were achieved. Density functional theory analysis of the configuration of the astaxanthin–βCD complex indicate that the hydroxyl hydrogen atoms on an ionone ring of astaxanthin interact with the oxygen atoms of βCD, but the ionone ring does not fit deeply within the βCD cavity. Notably, the astaxanthin–βCD complex exhibits higher thermal stability and antioxidant activity than free astaxanthin. The findings suggest that βCD encapsulation via the SAS process can produce astaxanthin microparticles with potential utility for food and pharmaceutical applications.

Photocatalytic Systems Based on ZnO Produced by Supercritical Antisolvent for Ceftriaxone Degradation

Emerging contaminants are a significant issue in the environment. Photocatalysis is proposed as a solution for the degradation of pollutants contained in wastewater. In this work, ZnO-based photocatalysts have been produced and tested for the photocatalytic degradation of an antibiotic; specifically, ceftriaxone has been used as a model contaminant. Moreover, there is particular interest in combining small-size ZnO particles and β-cyclodextrin (β-CD), creating a hybrid photocatalyst. Zinc acetate (ZnAc) (subsequently calcinated into ZnO) and β-CD particles with a mean diameter of 0.086 and 0.38 µm, respectively, were obtained using the supercritical antisolvent process (SAS). The produced photocatalysts include combinations of commercial and micronized particles of ZnO and β-CD and commercial and micronized ZnO. All the samples were characterized through UV–Vis diffuse reflectance spectroscopy (DRS), and the band gap values were calculated. Raman and FT-IR measurements confirmed the presence of ZnO and the existence of functional groups due to the β-cyclodextrin and ZnO combination in the hybrid photocatalysts. Wide-angle X-ray diffraction patterns proved that wurtzite is the main crystalline phase for all hybrid photocatalytic systems. In the photocatalytic degradation tests, it was observed that all the photocatalytic systems exhibited 100% removal efficiency within a few minutes. However, the commercial ZnO/micronized β-CD hybrid system is the photocatalyst that shows the best performance; in fact, when using this hybrid system, ceftriaxone was entirely degraded in 1 min.

Non-Isothermal Compressible Flow Model for Analyzing the Effect of High CO<sub>2</sub> Inlet Flow Rate on Particle Size in a Supercritical Antisolvent Process

In this work with CFD simulations, the evaluation of the supercritical anti-solvent (SAS) process for producing nanoparticles from an expanded solution of ethanol/solute in carbon dioxide is reported. The influence of the solution and antisolvent flow rates on mean particle size, the flow dynamic, and the supercritical mixture's jet velocity must be well established in the literature and analyzed. The high flow rate of the anti-solvent resulted in increased mean particle sizes for all studied cases. At the lowest flow rate of CO<sub>2</sub> examined, an increase in the solvent flow rate [0.3-1.0] ml/min initially led to a decrease of 11.2% in the mean particle diameter (MPD); however, further increasing the solvent flow rate [1.0-2.0]ml/min was an increase of 33% in this parameter. At the highest CO<sub>2</sub> flow rate, the behavior of MPS was the opposite; it had a rise de 13.5% in MPD with an increase in solvent flow rate; further increasing the flow rate of the solvent, there was a drop of 8.6% in MPD. Significant variations in the temperature lead to large fluctuations in the particle diameters. At last, the contact zones between CO<sub>2</sub> and ethanol were delimited, favoring the understanding of the influence of the flow patterns generated by the variation of the flow rates in the mean particle diameters.

Generation of Spherical Microparticles of Moringa Leaves through a Supercritical Antisolvent Extraction Process

The objective of this work was evaluation of the supercritical antisolvent extraction (SAE) process to generate microparticles with antioxidant activity from Moringa leaves. A biodegradable polymer was used as an inductor of particle precipitation. An ethanolic extract of 25 mg/mL was used in the SAE process, during which the influences of pressure (100–200 bar), temperature (35–55 °C) and extract–polymer ratio (0.11–0.33) on particle size and antioxidant activity were evaluated. An extract flow rate of 3 mL/min, a supercritical CO2 (scCO2) flow rate of 30 g CO2/min and a nozzle diameter of 100 µm were kept constant. The identification of several compounds of Moringa leaves, namely, coumaric acid and quercetin 3D glucoside, were determined with ultra-performance liquid chromatography coupled with mass spectrometry. The antioxidant activity of the extract and the precipitates was measured with 2,2-Diphenyl-1-picrylhydrazyl. Spherical microparticles with diameters in the range of 2–5 µm were obtained, with moderate antioxidant activity.

Preparation of inhalable quercetin-β-cyclodextrin inclusion complexes using the supercritical antisolvent process for the prevention of smoke inhalation-induced acute lung injury

Quercetin (Que) is a natural flavonoid with good anti-inflammatory and anti-apoptosis activities, but its poor water solubility and low bioavailability restrict its clinical application. Cyclodextrin inclusion is one effective method to improve the solubility of Que. In this study, Que-β-cyclodextrin inclusion complexes (Que-β-CD) were prepared using the supercritical antisolvent (SAS) process with supercritical carbon dioxide (SCCO2) and the grinding method, called S-Que-β-CD and G-Que-β-CD, respectively. Que-β-CD was identified with Fourier transform infrared spectroscopy and the X-ray diffraction method. S-Que-β-CD powders had a higher loading efficiency (19.81%) and drug release (71.76%), the smaller mass median aerodynamic diameter (2.83 µm), and the larger fine particle fraction (48.74%) than G-Que-β-CD powders, indicating the SAS process suitable for the preparation of Que-β-CD and S-Que-β-CD suitable for pulmonary inhalation. Pulmonary delivery of S-Que-β-CD showed good protection of the mouse lung from smoke inhalation-induced acute lung injury (SI-ALI), which was indicated by reduced pulmonary edema, high percutaneous oxygen saturation, weak inflammation and apoptosis, and the recovery of body weight. The SAS process is the optimal preparation method to obtain inhalable S-Que-β-CD powders with accelerated drug release, high lung deposition and enhanced therapeutic efficiency.

Solubility of probenecid in supercritical carbon dioxide and composite particles prepared using supercritical antisolvent process

The solubilities of probenecid in supercritical carbon dioxide (CO2) were measured in terms of mole fraction ranging from 0.13 × 10−5 to 1.45 × 10−5 at temperatures from 313.2 K to 353.2 K and pressures from 15 MPa to 31 MPa. The solubility data were correlated with the dimensionally consistent Chrastil equation, Garlapati and Madras equation, Mendez-Santiago and Teja equation, Kumar and Johnston equation, and the Peng-Robinson equation of state to deviations of 12.3 %, 6.7 %, 9.7 %, 8.1 %, and 16.2 %, respectively. Due to the low solubility nature, supercritical antisolvent (SAS) process was used for designing composite particles of probenecid and poly(lactide-co-glycolide) (PLGA). The effects of operating parameters on particle morphology, recovery and drug loading were studied. Through SAS, PLGA coated probenecid particles were successfully obtained. The recovery could be higher than 80 %, and the probenecid concentration could be up to 75 mg/mL. Moreover, results of dissolution studies reveal the PLGA coated composite particles can accelerate the dissolution rate by about 10 and 2.4 times, comparing with the unprocessed probenecid and SAS-processed probenecid without PLGA.