Rapid Expansion Of Supercritical Solutions Research Articles

Application of Box-Behnken Design in microparticle production of p-Toluenesulfonamide through the rapid expansion of supercritical solutions process

p-Toluenesulfonamide (PTS) is a developing small molecular anticancer agent with good lipophilic ability. Microparticle production of PTS is an approach to enhance the dissolution profile and explore the potential for novel drug delivery system design. This study employed the rapid expansion of supercritical solutions (RESS) process to produce microparticles of PTS using supercritical carbon dioxide as the solvent. To meet the concept of quality by design in the pharmaceutical industry, the effects of process parameters in RESS operation were investigated and optimized by a design of experiments approach, the Box-Behnken Design (BBD). The design space for microparticle production of PTS was shown, and the analysis of variance (ANOVA) confirmed the significance of process parameters. According to the BBD study, at the optimal operating condition, PTS microparticles were successfully generated from the unprocessed mean size of 240.3 μm to 1.3 μm. The solid-state property of the unprocessed and micronized PTS powders was compared and confirmed consistent through the PXRD, DSC, and FTIR analysis. Finally, the dissolution profiles of PTS before and after the RESS process were determined, and the dissolution rate of RESS-produced PTS microparticles was enhanced 1500 times compared with the unprocessed PTS.

Solubility measurement and modeling of hydroxychloroquine sulfate (antimalarial medication) in supercritical carbon dioxide

A supercritical fluid, such as supercritical carbon dioxide (scCO2) is increasingly used for the micronization of pharmaceuticals in the recent past. The role of scCO2 as a green solvent in supercritical fluid (SCF) process is decided by the solubility information of the pharmaceutical compound in scCO2. The commonly used SCF processes are the rapid expansion of supercritical solution (RESS) and supercritical antisolvent precipitation (SAS). To implement micronization process, solubility of pharmaceuticals in scCO2 is required. Present study is aimed at both measuring and modeling of solubilities of hydroxychloroquine sulfate (HCQS) in scCO2. Experiments were conducted at various conditions (P = 12 to 27 MPa and T = 308 to 338 K), for the first time. The measured solubilities were found to be ranging between (0.0304 × 10–4 and 0.1459 × 10–4) at 308 K, (0.0627 × 10–4 and 0.3158 × 10–4) at 318 K, (0.0982 × 10–4 and 0.4351 × 10–4) at 328 K, (0.1398 × 10–4 and 0.5515 × 10–4) at 338 K. To expand the usage of the data, various models were tested. For the modelling task existing models (Chrastil, reformulated Chrastil, Méndez-Santiago and Teja (MST), Bartle et al., Reddy-Garlapati, Sodeifian et al., models) and new set of solvate complex models were considered. Among the all models investigated Reddy-Garlapati and new solvate complex models are able to fit the data with the least error. Finally, the total and solvation enthalpies of HCQS in scCO2 were calculated with the help of model constants obtained from Chrastil, reformulated Chrastil and Bartle et al., models.

Enhanced thermal conductivity of polyamide nanocomposites involving expanded graphite–carbon nanotube network structure using supercritical CO2

In this study, supercritical carbon dioxide (scCO2) was used to form a network structure of expanded graphite (EG) and multi-walled carbon nanotube (MWCNT) to achieve high thermal conductivity. Continuous processes, such as supercritical drying and rapid expansion of supercritical solutions were applied to pristine graphite and MWCNT. Polyamide 6 (PA6) nanocomposites with scCO2-treated EG and MWCNT were prepared by twin-screw extruder-based melt compounding. In the PA6 nanocomposites, the EG sheets were homogenously dispersed, while the MWCNTs were located between the EG sheets, thereby acting as a bridge for the EG. Subsequently, the 35 wt.% imbedding in PA6 nanocomposite had an effective heat transfer pathway and high thermal conductivity (2.12 W m−1 K−1). It was observed that supercritical fluid processing is a facile and effective strategy to improve the thermal conductivity of polymer nanocomposites.

Supercritical carbon dioxide solubility measurement and modelling for effective size reduction of nifedipine particles for transdermal application

Nifedipine (NIF) is a Class II drug of the Biopharmaceutical Classification System (BCS) with low oral bioavailability, low dissolution rate and significant hepatic drug metabolism. The transdermal route using supersaturated systems could be considered. For this purpose, physicochemical properties of NIF such as its dissolution rate, may be a limiting factor and must be improved. Crystallization processes assisted by supercritical carbon dioxide (scCO2) and particularly the Rapid Expansion of Supercritical Solution (RESS) process may improve drug bioavailability by reducing particle size and consequently increasing surface area. This study addresses the reduction of NIF particle size using scCO2-RESS as crystallization process. Experimental solubility studies were performed at different temperature (308 and 318 K) and pressure ranges (9–24 MPa). Solubility data were correlated with two thermodynamic models in order to predict NIF solubility in scCO2. Optimized operating conditions, identified by thermodynamic modelling, allowed the production of thinner NIF particles and a size reduction up to ten fold. Particle size reduction improved NIF dissolution kinetics in aqueous medium: after 90 min, 42 % of raw NIF was released against 80 % for crystallized NIF. The scCO2-RESS process is a solvent free process, that can produce micronized or nanosized crystals able to improve physicochemical properties of poorly water-soluble drugs.

Solubility and thermodynamic modeling of sildenafil citrate in supercritical carbon dioxide

Determining the solubility of drugs in supercritical carbon dioxide (SC-CO2) is crucial to select an adequate SC-CO2 assisted technique (e.g., supercritical anti-solvent, rapid expansion of supercritical solution, etc.) to produce micro or nano sized drug particles. In this study, the solubility of sildenafil citrate (SLC) in SC-CO2 using a static method was measured and modeled for the first time. For this purpose, experiments to measure the solubility of SLC in SC-CO2 were carried out at different temperature (308 to 338 K) and pressure values (12 to 30 MPa). The solubility expressed as molar fraction and g/L of SLC in SC-CO2 was quantified in the range of 2.40 × 10−7 to 6.48 × 10−6 and 0.001 to 0.079 (g/L), respectively. Various models were used to correlate the measured solubility data, including the Soave Redlich Kwong (AARD = 14.33) and PC-SAFT theory (AARD =10.26) equations of state (EoS), the Modified Wilson's model (AARD=7.80), and Chrastil (AARD = 7.90), Bartle et al. (AARD = 8.75), Méndez-Santiago-Teja (AARD = 6.50), and Kumar-Johnston (AARD =5.30) as the density-based semi-empirical models. Finally, the approximate values of total (ΔHtotal), vaporization (ΔHvap), and solvation (ΔHsol) enthalpies were computed.

Solid solubility measurement of haloperidol in supercritical carbon dioxide and nanonization using the rapid expansion of supercritical solutions process

Haloperidol is a poorly water-soluble drug, and its efficacy was limited by dissolution behavior. This study aimed to improve haloperidol’s dissolution rate by nanonization using rapid expansion of supercritical solution (RESS) process. To design RESS, the solubility data of haloperidol in supercritical CO2 were measured and reported from 3.4 × 10−7 to 1.4 × 10−5 in mole fraction at temperatures from 313.2 K to 333.2 K and pressure up to 22 MPa. The measured solubility data were then correlated using semi-empirical equations with average absolute relative deviations less than 5%. For RESS study, the effects of operating parameters were compared and discussed. The crystal habit of haloperidol was modified from irregular to spherical, and the mean particle size was reduced to 300 nm. Improvement of the dissolution rate was finally verified, and the dissolution rate of haloperidol was enhanced 74 times after the RESS processing.

Nanoparticle Production of Zingiber officinale Roscoe Rhizome Extracts by ESS (Expansion of Supercritical Solution)

Aims: To propose a modified RESS method of herbal pharmaceutical extracts nanoparticle production. Background: A vast number of methods have been applied to water-insoluble pharmaceuticals to improve their solubility. Nanoparticle production of pharmaceuticals is considered as one of the high-speed ways to improve solubility. Objective: Supercritical CO2 was applied to extract Zingiber officinale Roscoe rhizome pharmaceutical. Then, a modified RESS (Rapid Expansion of Supercritical Solution) method, called ESS (Expansion of Supercritical Solution), was exerted to obtain NPs (nanoparticles) of the extracted pharmaceuticals. Methods: Initially, applying high pressure in supercritical CO2 contributed to the extract dissolution such that supercritical CO2 was saturated with the sample. Then, by decreasing the pressure, an expansion occurred in the saturated medium. This expansion reduced the power of supercritical CO2 solvent and induced the sample nanoparticle nucleation in the needle valve. Results: LC-MS (Liquid Chromatography-Mass Spectrometry) and EDX (energy dispersive X-ray spectroscopy) result provided solid evidence for the presence of anti-cancer pharmaceutical, [6]-Gingerol, in the extract. The medium size of the nanoparticles in FESEM (Field Emission Scanning Electron Microscopy) analysis was 36 nm. The most satisfactory parameters for a 2 mg mL-1 feeding solution were the initial pressure of 350 atm, secondary pressure of 160 atm, equilibrating time of 10 min, precipitating time of 20 min, and temperature of 48 °C. Conclusion: Unlike rapid expansion of supercritical solution methodology, in this technique, the initial and secondary pressures were permanently above the critical pressure to provide a gentle expansion, which contributes to the production of uniform and small particles. The obtained uniform NPs had a narrow size distribution. Consequently, ESS technique can be considered as an efficient technique for improving the solubility of hydrophobic pharmaceuticals, such as [6]-gingerol.

Nanoparticle size control of theophylline using rapid expansion of supercritical solutions (RESS) technique

This paper presents the strategy for nanoparticle design of theophylline using rapid expansion of supercritical solutions (RESS) technique. In this study, the production of nanoparticles of theophylline via the RESS technique using supercritical CO2 has been presented. The effects of five different operating parameters including equilibrium temperatures (313.2, 323.2, and 338.2 K), equilibrium pressures (14.0–22.0 MPa), pre-expansion temperatures (333.2–373.2 K), nozzle temperatures (323.2–383.2 K), and collection temperatures (265–303 K) on the size and morphology of the nanoparticles were investigated. The mean size of the produced particle was in the range of 200–300 nm, which was about 1/300 of the size of the unprocessed particle. Furthermore, the results of summarizing the dependence of the five operating parameters on particle size showed that nanoparticle size was strongly influenced by supersaturation between the pre-expansion and post-expansion sections. The supersaturation-based design will enable the control of nanoparticle size produced using the RESS technique.

Improving the dissolution of lidocaine by dispersing the rapid expansion of supercritical solution

An experimental study of the grinding of lidocaine by the rapid expansion of supercritical solutions (RESS method) was carried out. The experiments were carried out in the pressure range of 10-35 MPa and temperatures of 308-333 K. The analysis of the morphology and size of particles, as well as the effect of the process parameters on them, was carried out. Qualitative and quantitative spectrophotometric analysis was carried out. The dissolution test was carried out in a phosphate buffered saline medium simulating plasma, which showed that the reduction in particle size gave an increased yield of the drug in a shorter period of time compared to the original drug that was not treated. Keywords: supercritical fluid, microparticles, spectrophotometric analysis, lidocaine.

Venturi-based rapid expansion of supercritical solution (Vent-RESS): synthesis of liposomes for pH-triggered delivery of hydrophilic and lipophilic bioactives.

Multivitamin-loaded and surface-modified liposomes tailored for simultaneous intestinal delivery of both lipophilic and hydrophilic bioactives were synthesized from sunflower phosphatidylcholine (SFPC). Liposomes (SL) were generated with the aid of a novel, organic solvent free, and environmentally benign process which utilizes venturi-based rapid expansion of supercritical solution (Vent-RESS). Vitamins E and C were used as model lipophilic and hydrophilic bioactives and demonstrated an average encapsulation efficiency of 92 and 70 %, respectively. Synthesized liposomes were coated with a pH-responsive double-wall of chitosan and β-lactoglobulin (βlg-Cs-SL) to develop a biocompatible vehicle for pH-triggered delivery of bioactive cargo(s). To compare the efficacy of this newly developed dual-coating, SL was also coated with a commercially available pH responsive polymer, Eudragit® S100 (Eu-SL). No organic solvent was used during the surface coating of SLs with these two different types of enteric coatings. The performance of these two coatings was studied by conducting morphological characterization through diameter and ζ-potential measurements along with confocal laser scanning and freeze-fracture cryogenic scanning electron microscopies. The stability of coated and uncoated SFPC liposomes was determined in simulated gastrointestinal fluids. For βlg-Cs-SL and Eu-SL, after 2 h of incubation in simulated gastric condition, less than 5 % of the encapsulated vitamins C and E were released, whereas for SL, 41 and 28 % of vitamins C and E were released within 2 h of incubation period. In simulated intestinal fluid, coated liposomes released most of their remaining payload when incubated for 4 h. The newly developed dual coating was found to be as effective as its commercially available counterpart, Eudragit® S100 coating; nevertheless, the biocompatible, non-toxic, and non-synthetic nature of this coating makes it an attractive alternative. Modeling the release kinetics of vitamins from coated liposome showed that the release of payload from surface coated liposomes proceeded through a multistep structural disintegration involving both Fickian and non-Fickian types of diffusion. The ability of these surface-coated liposomes to maintain structural integrity under the gastric condition followed by site-specific, pH-triggered release of encapsulated cargo in the intestine will make them highly suitable for oral administration of bioactive compounds in pharmaceutical and food applications.

CO2 utilization as a supercritical solvent and supercritical antisolvent in production of sertraline hydrochloride nanoparticles

Supercritical fluid (SCF) processes have attracted great attention for fabricating micro and nanoparticles in the pharmaceutical applications. Herein we utilized, for the first time, Gas Anti-Solvent (GAS) and Rapid Expansion of Supercritical Solution with Solid Cosolvent (RESS-SC) processes to fabricate nanoparticles of sertraline hydrochloride (SRT), a widespread antidepressant. Design of experiment (DoE) was implemented to evaluate the influences of various operating conditions and find an optimal combination of the conditions to achieve the smallest particle size (PS). Variations of the physical and chemical properties were studied by performing FTIR, FESEM, DLS, XRD, and DSC analyses as well as dissolution rate tests. By reducing the particle size from about 50 μm to 102 ± 11 nm at low pressures, the results showed the superiority of GAS compared to RESS-SC with a minimum particle size of 185 ± 9 nm. Furthermore, the GAS and RESS-SC methods led to dissolution rates that were 50 and 18 times greater than that of the original SRT, respectively.

Broadband microwave absorption performance and theoretical dielectric properties model of hollow porous carbon spheres/expanded polypropylene composite foams

Hollow porous carbon spheres (HPCS)/Expanded polypropylene (EPP) composite foams were prepared by rapid expansion of supercritical solution and steam chest molding. Due to the uniform and continuous foam structure, HPCS/EPP foams can maintain better loss ability at lower permittivity. Excellent impedance matching enables them to achieve ultra-broad absorption bandwidth of over 17 GHz. Furthermore, the high frequency dielectric properties of HPCS/EPP foams with unique dual percolation microstructure were described by the Two Exponent Phenomenological Percolation Equation (TEPPE) in a two-step framework. It was revealed that the fitting values of the complex permittivity of the foams with different expansion ratios are in good agreement with the experimental values in the frequency band from 0.5 to 18 GHz. This work introduces a new approach for predicting and optimizing the electromagnetic properties of ternary foamed composites.

Nanoparticle Production of Terminalia Chebula Extracts by Expansion of Supercritical Solution (ESS)

Terminalia chebula pharmaceuticals were extracted by using the supercritical fluid extraction (SFE) technique. Under the optimal conditions of 184 [Formula: see text]L modifier volume, 46 min dynamic extraction time, and 316 atm fluid pressure, the extraction procedure was optimized by central composite design. A modified rapid expansion of supercritical solution (RESS) technique, named expansion of the supercritical solution (ESS) was used to create the extracted pharmaceutical nanoparticles (NPs). In ESS, supercritical carbon dioxide (SC-CO[Formula: see text] was saturated with the extracts at high-pressure. Next, a pressure drop reduced the SC-CO2 solubility power in a way the extracts started to precipitate. In contrast to RESS, the pressure was permanently conserved above the critical pressure before and after depressurization. Therefore, the expansion process was gentle, which led to obtaining small and uniform particles. In the NP production process, the most adequate parameters were 360[Formula: see text]atm premier pressure, 120[Formula: see text]atm subsequent pressure, 25[Formula: see text]min equilibrium time, 30[Formula: see text]min sedimentation time, and [Formula: see text]C temperature. The average size of precipitated NPs was 41[Formula: see text]nm according to the results of field emission scanning electron microscopy analysis. The liquid chromatography-mass spectrometry evaluation demonstrated the presence of chebulinic and chebulagic acids in the extracted sample.

Preparation of stable nanosuspensions from Asplenium scolopendrium leaves via rapid expansion of supercritical solution into aqueous solutions (RESSAS)

The present study intended to stabilize the nanosuspension of powerful antioxidants such as genistein, quercetin, as well as caffeic acid from the leaves related to Asplenium scolopendrium by utilizing the RESSAS process. These compounds offer low efficacy and bioavailability since they are barely soluble in aqueous media. Thus, producing stable nanosuspensions can resolve this problem by reducing the size of the particle. In addition, central composite design (CCD) was used for analyzing the impact of oven temperature, pressure, CO2 flow rate, and modifier volume on the antioxidant activity index (AAI) in the outcome of RESSAS process. Further, DLS, FE-SEM, and LC-MS techniques were implemented for evaluating the nanosuspension features. Based on the results, the behavior of the particles after forming particle was emphasized, which indicated that the RESSAS process results in diminished agglomeration of the particle and enhanced AAI for the extract. Thus, the bioavailability of the products related to herbal medicinal can be dramatically increased in biological media.

Preparation of liposomes composed of supercritical carbon dioxide-philic phospholipids using the rapid expansion of supercritical solution process

The synthesis of supercritical carbon dioxide-philic phospholipids allowed the vitamin E acetate (VEA) liposomes composed of them to be successfully prepared using the rapid expansion of supercritical solution (RESS) process without any organic solvent. The single-factor analysis and the response surface methodology combined with Box–Behnken design were used to optimize the operation conditions. The results indicated that pressure was the most important factor to the encapsulation efficiency of the liposomes, which was increased with a higher pressure. Temperature and mass ratio also had some effects, while the interaction of the three factors was not significant. The liposomes prepared under the optimal conditions (i.e., temperature of 55.45 °C, pressure of 25.00 MPa, and mass ratio of 6.35:1) showed good stability as well as the slow and continuous release behavior. The encapsulation efficiency, average particle size, PDI, and zeta-potential of the prepared liposomes were 92.84 ± 0.98%, 247.4 ± 6.5 nm, 0.295 ± 0.012, and −42.55 ± 0.64 mV, respectively.

Rapid expansion supercritical solution (RESS) of CO2 as a green technology method for pineapple peels solid oil particle formation

Current development using the technique of Rapid Expansion Supercritical Solution (RESS) in solid oil particle formation pineapple peel contains a great deal active pharmacological which are anti-inflammatory, anti-oxidants, and anti-cancer agent. Many researchers use the conventional technique such as hydro-distillation, supercritical fluid extraction, and soxhlet extraction in order to extract the valuable component in oil formed. However, these techniques have several disadvantages such as long extraction time, high usage of solvent and produce toxic residual which can harm the environment. The RESS technique is not as time consuming as it will directly produce oil in particle formation, instead of conventional technique that need to undergo further technique such as spray drying in order to produce solid oil particle. In this study the extraction was conducted using temperature 40, 45, 50, 55, 60°C and the pressure used were 3000, 4000, 5000, 6000 and 7000 psi at a constant flowrate of 24ml/min for 50 minutes extraction time. The extracted component in solid oil particle was analyzed using Gas Chromatography Mass Spectrometry (GCMS) and show that pineapple peels is rich in volatile components such as 1-Hexene, 4-methyl, Benzene, 1,1’-(1,2 cyclobutanediyl) bis-, trans, and 1-Buten-3-one, 1-(2-carboxy-4,4-dimethylcyclobutenyl).

Numerical solution of particle size distribution equation: Rapid expansion of supercritical solution (RESS) process

The present study aimed to numerically simulate the rapid expansion of the supercritical solution (RESS) process including particle generation, hydrodynamics, and solving the population balance equation (PBE) to predict the particle-size distribution (PSD) of solid-supercritical carbon dioxide binary systems. Energy, momentum, and mass equations, in addition to the extended generalized Bender equation of state (EoS), were applied to predict the hydrodynamic behavior of a supercritical solution under several operating conditions using a nozzle and expansion vessel. The tetraphenylporphyrin (TBTPP) solubility in supercritical carbon dioxide was calculated using the Peng–Robinson EoS/Kwak–Mansoori as a mixing rule. Subsequently, TBTPP, aspirin, ibuprofen, and salicylic acid nucleation as well as the supersaturation rate were calculated. Finally, we solved the time dependence of the parameters of the size distribution numerically. The established models are compared over a wide parameter range using a reference model that refers to the method of moment log-normal size distribution functions through the RESS process to predict a solid PSD. The results obtained are presented with and without coagulation phenomena. The average absolute percent deviation of solubility of TBTPP was 3.98, and the hydrodynamic behavior of supercritical carbon dioxide showed a similar trend as the results presented in the published research work. Furthermore, a particle size distribution prediction using coagulation showed acceptable agreement with the experimental PSDs.

Particle Size Reduction Techniques of Pharmaceutical Compounds for the Enhancement of Their Dissolution Rate and Bioavailability

In pharmaceutical research and development, various new chemical entities (NCE) are found to be poorly water-soluble. Therefore, solubility enhancement, a key factor for higher bioavailability, is a major challenge in pharmaceutical industries. Particle size reduction is one such method that increases the surface area of the pharmaceutical compounds and subsequently leads to a higher dissolution rate and bioavailability. Conventional processes such as milling, high-pressure homogenization, and spray drying are well established and widely used for particle size reduction. However, a few disadvantages such as a broader particle size distribution (PSD) and thermal and chemical degradation of the product are major concerns for the product quality. Non-conventional processes such as liquid anti-solvent crystallization, supercritical anti-solvent process, rapid expansion of supercritical solutions, particles from gas saturated solutions, and pulsed laser ablation are emerging as potential alternatives to overcome the disadvantages of conventional processes. This review critically summarizes the milling, spray drying, high-pressure homogenization, liquid anti-solvent crystallization, spray freeze-drying, supercritical carbon dioxide $$(\mathrm{SC C}{\mathrm{O}}_{2})$$ –based micronization processes, pulsed laser ablation and combinative techniques. The success of these processes in enhancing the dissolution rate and bioavailability of many active pharmaceutical ingredients (APIs) has been critically examined. The advantages and limitations of these processes are also discussed. Finally, opportunities for future research are also proposed.

Улучшение растворения лидокаина посредством диспергирования методом быстрого расширения сверхкритического раствора

An experimental study of the grinding of lidocaine by the rapid expansion of supercritical solutions (RESS method) was carried out. The experiments were carried out in the pressure range of 10–35 MPa and temperatures of 308–333 K. The analysis of the morphology and size of particles, as well as the effect of the process parameters on them, was carried out. Qualitative and quantitative spectrophotometric analysis was carried out. The dissolution test was carried out in a phosphate buffered saline medium simulating plasma, which showed that the reduction in particle size gave an increased yield of the drug in a shorter period of time compared to the original drug that was not treated.

Response Surface Optimization of Catechin Liposomes Preparation Using the Rapid Expansion of Supercritical Solution Process.

Phospholipid liposomes are a promising drug delivery system. Catechin, a hydrophilic drug, was used to prepare catechin liposomes through a modified rapid expansion of supercritical solution (RESS) process in this study. The influences of operation parameters (i.e., temperature, pressure, and mass ratio of liposomal materials to catechin) on the properties of the prepared liposomes were determined using the single-factor analysis. The process was further optimized by response surface methodology (RSM) based on the Box-Behnken design (BBD). The encapsulation efficiency (EE) values can be adequately predicted using the obtained equation. The maximum EE value can reach 61.36±0.68% under the optimal parameters (i.e., the expansion temperature, pressure, and p/c mass ratio were 56.34 °C, 19.99 MPa, and 5.99, respectively). The prepared liposomes can effectively protect and stabilize the loaded catechin effectively. In addition, the in vitro release study showed the slow and sustained release behavior of the catechin liposomes.