Exploring the Effects of Process Parameters during W/O/W Emulsion Preparation and Supercritical Fluid Extraction on the Protein Encapsulation and Release Properties of PLGA Microspheres.

In this study, protein-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared via supercritical fluid extraction of emulsion (SFEE) technology. To understand the correlation between process parameters and the main quality characteristics of PLGA microspheres, a comprehensive prior study on the influence of process variables on encapsulation efficiency (EE), initial drug burst release (IBR), morphology, surface property, and particle size distribution (PSD) was conducted within a wide process condition range of each unit process step, from the double-emulsion preparation step to the extraction step. Bovine serum albumin (BSA), a high-molecular weight-protein that is difficult to control the IBR and EE of PLGA microspheres with, was used as a model material. As double-emulsion manufacturing process parameters, the primary (W/O) and secondary emulsion (W/O/W) homogenization speed and secondary emulsification time were evaluated. In addition, the effect of the SFEE process parameters, including the pressure (70-160 bar), temperature (35-65 °C), stirring rate (50-1000 rpm), and flow rate of supercritical carbon dioxide, SC-CO2 (1-40 mL/min), on PLGA microsphere quality properties were also evaluated. An increase in the homogenization speed of the primary emulsion resulted in an increase in EE and a decrease in IBR. In contrast, increasing the secondary emulsification speed resulted in a decrease in EE and an increase in IBR along with a decrease in microsphere size. The insufficient secondary emulsification time resulted in excessive increases in particle size, and excessive durations resulted in decreased EE and increased IBR. Increasing the temperature and pressure of SFEE resulted in an overall increase in particle size, a decrease in EE, and an increase in IBR. It was observed that, at low stirring rates or SC-CO2 flow rates, there was an increase in particle size and SPAN value, while the EE decreased. Overall, when the EE of the prepared microspheres is low, a higher proportion of drugs is distributed on the external surface of the microspheres, resulting in a larger IBR. In conclusion, this study contributes to the scientific understanding of the influence of SFEE process variables on PLGA microspheres.

Toxic Gas and Smoke Generation and Flammability of Flame-Retardant Plywood.

Limited by flammability, wood and wood-based materials face challenges in distinguishing themselves as structural materials or finishing materials. Once burning, they can produce toxic gases detrimental to humans and the environment. Therefore, it is critical to make clear whether fire-retardant wood construction materials are insusceptible to fire and not the sources of toxic gases. This study aimed to evaluate flame-retardant plywood from the aspects of flammability and the toxic gas and smoke generation during combustion. The flame-retardant plywood was manufactured by impregnating a flame-retardant resin in line with International Maritime Organization (IMO) standards. The research results indicate that seven out of the eight kinds of toxic gases listed by the IMO, other than CO, were not detected during the combustion of the flame-retardant plywood. While CO was detected, its quantities under three test conditions are below the corresponding thresholds. Therefore, unlike synthetic resin products, flame-retardant plywood is a promising finishing material that can reduce the damage from toxic gases in the event of a fire. In the smoke generation tests, the mass reduction rate of flame-retardant plywood increased from 13% to 18% and then to 20% as the test condition became more severe. Under the same circumstances, the average maximum specific optical density also followed an upward trend, whose values (75.70, 81.00, and 191.20), however, still met the IMO standard of below 200. This reflects that the flame-retardant plywood is competent as a finishing material. Further, flammability was evaluated, and the critical flux at extinguishment (CFE), total heat release (Qt), and peak heat release rate (Qp) were determined to be 49.5 kW/m2, 0.21 MJ, and 0.66 kW, respectively, which all did not reach the corresponding thresholds given by the IMO. To sum up, flame-retardant plywood has satisfactory flame-retardant performance and meets fire safety standards, showing the potential to be an attractive finishing material for building and construction.

Evaluation of deep learning-based quantitative computed tomography for opportunistic osteoporosis screening.

To evaluate diagnostic efficacy of deep learning (DL)-based automated bone mineral density (BMD) measurement for opportunistic screening of osteoporosis with routine computed tomography (CT) scans. A DL-based automated quantitative computed tomography (DL-QCT) solution was evaluated with 112 routine clinical CT scans from 84 patients who underwent either chest (N:39), lumbar spine (N:34), or abdominal CT (N:39) scan. The automated BMD measurements (DL-BMD) on L1 and L2 vertebral bodies from DL-QCT were validated with manual BMD (m-BMD) measurement from conventional asynchronous QCT using Pearson's correlation and intraclass correlation. Receiver operating characteristic curve (ROC) analysis identified the diagnostic ability of DL-BMD for low BMD and osteoporosis, determined by dual-energy X-ray absorptiometry (DXA) and m-BMD. Excellent concordance were seen between m-BMD and DL-BMD in total CT scans (r = 0.961/0.979). The ROC-derived AUC of DL-BMD compared to that of central DXA for the low-BMD and osteoporosis patients was 0.847 and 0.770 respectively. The sensitivity, specificity, and accuracy of DL-BMD compared to central DXA for low BMD were 75.0%, 75.0%, and 75.0%, respectively, and those for osteoporosis were 68.0%, 80.5%, and 77.7%. The AUC of DL-BMD compared to the m-BMD for low BMD and osteoporosis diagnosis were 0.990 and 0.943, respectively. The sensitivity, specificity, and accuracy of DL-BMD compared to m-BMD for low BMD were 95.5%, 93.5%, and 94.6%, and those for osteoporosis were 88.2%, 94.5%, and 92.9%, respectively. DL-BMD exhibited excellent agreement with m-BMD on L1 and L2 vertebrae in the various routine clinical CT scans and had comparable diagnostic performance for detecting the low-BMD and osteoporosis on conventional QCT.

Enhancing safety of construction workers in Korea: an integrated text mining and machine learning framework for predicting accident types.

Construction workers face a high risk of various occupational accidents, many of which can result in fatalities. This study aims to develop a prediction model for nine prevalent types of construction accidents, utilizing construction tasks, activities, and tools/materials as input features, through the application of machine learning-based multi-class classification algorithms. 152,867 construction accident summary reports, composed of both structured (construction task, construction activity, accident type) and unstructured data (tools/materials) were used for the study. The study employed several data processing techniques, including keyword extraction through text mining, Boruta feature selection, and SMOTE data resampling enhance model accuracy. Three performance metrics (Multi-class area under the receiver operating characteristic curve (MAUC), Multi-class Matthews Correlation Coefficient (MMCC), Geometric-mean (G-mean)) were used to compare the predictive performance of four machine learning algorithms, including Decision tree, Random forest, Naïve bayes, and XGBoost. Of the four algorithms, XGBoost showed the highest performance in predicting accident type (MAUC: 0.8603, MMCC: 0.3523, G-mean: 0.5009). Furthermore, a Shapley additive explanation (SHAP) analysis was conducted to visualize feature importance. The findings of this study make a valuable contribution to improving construction safety by presenting a prediction model for accident types derived from real-world big data.

Quenching of a no-insulation high-temperature superconducting magnet.

We report details on the quenching incident of an 18 T high-temperature superconducting (HTS) magnet, which occurred in December 2020. It has been received that the no-insulation (NI) design of an HTS magnet is relatively safe in quenching. However, the NI design could not completely prevent the magnet from quenching and damaging the associated system. Due to significant vibrations and fast energy dissipation during quenching, the magnet and the detector components are seriously damaged. The manufacturer inspected the magnet after the incident and repaired it in the spring of 2021. The magnet showed stable and consistent performance after the repair. It is evident that the NI-HTS magnet still requires quench protection circuits to secure the magnet and associated system.

Preparation of Hot-Melt-Extruded Solid Dispersion Based on Pre-Formulation Strategies and Its Enhanced Therapeutic Efficacy.

In this study, an amorphous solid dispersion containing the poorly water-soluble drug, bisacodyl, was prepared by hot-melt extrusion to enhance its therapeutic efficacy. First, the miscibility and interaction between the drug and polymer were investigated as pre-formulation strategies using various analytical approaches to obtain information for selecting a suitable polymer. Based on the calculation of the Hansen solubility parameter and the identification of the single glass transition temperature (Tg), the miscibility between bisacodyl and all the investigated polymers was confirmed. Additionally, the drug-polymer molecular interaction was identified based on the comprehensive results of dynamic vapor sorption (DVS), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, and a comparison of the predicted and experimental values of Tg. In particular, the hydroxypropyl methylcellulose (HPMC)-based solid dispersions, which exhibited large deviation between the calculated and experimental values of Tg and superior physical stability after DVS experiments, were selected as the most appropriate solubilized bisacodyl formulations due to the excellent inhibitory effects on precipitation based on the results of the non-sink dissolution test. Furthermore, it was shown that the enteric-coated tablets containing HPMC-bisacodyl at a 1:4 ratio (w/w) had significantly improved in vivo therapeutic laxative efficacy compared to preparations containing un-solubilized raw bisacodyl in constipation-induced rabbits. Therefore, it was concluded that the pre-formulation strategy, using several analyses and approaches, was successfully applied in this study to investigate the miscibility and interaction of drug-polymer systems, hence resulting in the manufacture of favorable solid dispersions with favorable in vitro and in vivo performances using hot-melt extrusion processes.

Effect of eardrum perforation and chronic otitis media on the results of infrared tympanic thermometer in adults: A systematic review and meta-analysis.

BACKGROUND: This study was conducted to determine whether tympanic membrane perforation or chronic otitis media affects the results of an infrared tympanic membrane thermometer in adults. METHODS: A literature search was performed using PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar. RESULTS: Four nonrandomized studies were included in the analysis. The temperatures of the bilateral eardrums (one eardrum with normal condition [control group] and the other eardrum with perforation or chronic otitis media [experimental group]) were measured for the same subject in the studies. The mean and standard deviation of the bilateral tympanic membrane temperatures were used to calculate the mean difference (MD) with a corresponding 95% confidence interval (CI). The fixed-effect model was utilized based on the results of the heterogeneity measurement using the Chi2 test and I2 statistic. The results of a meta-analysis in the normal eardrum (control group) and perforated eardrum, chronic suppurative otitis media with tympanic membrane perforation, or chronic otitis media with cholesteatoma (experimental group) were 343 subjects (MD = 0.05; 95% CI = -0.00 to 0.11; P = .06). A meta-analysis of the normal eardrum (control group) and perforated eardrum or chronic suppurative otitis media with tympanic membrane perforation except for cholesteatoma (experimental group) found 296 subjects (MD = 0.05; 95% CI = -0.01 to 0.11; P = .10). CONCLUSION: When the temperatures of the bilateral eardrums were measured using an infrared tympanic membrane thermometer, no difference was observed between the eardrum with perforation or chronic otitis media and the normal eardrum.

Preparation of Organic-Inorganic Phosphorus-Nitrogen-Based Flame Retardants and Their Application to Plywood.

The combustibility of wood can be improved by physical and chemical means, thus expanding the use of wood products. In this study, two novel phosphorus-nitrogen flame retardants (UCPR and MCPR) were developed, and the intercalated modified layered double hydroxides (LDH) thereof were designated as UCPR-LDH and MCPR-LDH. By impregnating poplar veneer with UCPR-LDH and MCPR-LDH solutions, the study investigated the effects of different concentrations (1%, 5%, 10%), processes (vacuum-pressure impregnation, room temperature impregnation, normal-pressure impregnation), and impregnation times (2 h, 3 h, 24 h, 48 h) on the weight-gain rate of veneer. The optimal process was then selected for preparing formaldehyde-free three-layer plywood. Nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) were used to characterize the UCPR and MCPR. Meanwhile, gel-permeation chromatography (GPC) demonstrated that the molecular weight of the synthesized flame retardants increased as their molecular distribution became more uniform. The impregnation process was performed at normal temperature and pressure for 48 h at a 5% flame retardant concentration. Results from cone calorimetry indicate that the UCPR-LDH plywood exhibits a peak heat release rate that is 30.43% lower than that of the control group, demonstrating superior thermal barrier performance. The smoke emission of the MCPR-LDH plywood was reduced by 33.62% compared to the control group, indicating superior smoke suppression performance. This method presents a viable approach for synthesizing organic-inorganic flame retardants.

Ultrasonographic Localization of Parotid Gland Tumor Relative to the Facial Nerve Using Stensen's Duct Criterion.

PURPOSE: During the preoperative evaluation of parotid gland tumors, one of the main concerns is to determine the location of the tumors in relation to the facial nerve. This study aims to assess the value of ultrasound for determining the location of parotid gland tumors in relation to the facial nerve using Stensen's duct. METHODS: This is a retrospective cross-sectional study at a single institute. The subjects who underwent preoperative ultrasound and parotidectomy for parotid gland tumors were included. The subjects with incomplete operative records or no reference standard for the location of parotid gland tumor were excluded. The primary predictor was ultrasound tumor location, which was defined as the location of parotid gland tumors determined by preoperative ultrasound as to whether the tumors were superficial or deep to the facial nerve. The operative records were used as the reference standard for the location of parotid gland tumors. The primary outcome was diagnostic performances of preoperative ultrasound in predicting the location of parotid gland tumors, which were calculated by comparing ultrasound tumor location to the reference standard. Covariates were sex, age, type of surgery, tumor size, and tumor histology. Data analysis involved descriptive and analytic statistics; P < .05 was considered statistically significant. RESULTS: One hundred and two of 140 eligible subjects met inclusion and exclusion criteria. There were 50 male and 52 female, with a mean age of 53.3 years. Ultrasound tumor location was classified as deep in 29 subjects, superficial in 50, and indeterminate in 23. The reference standard was deep in 32 subjects and superficial in 70. Indeterminate ultrasound tumor location results were grouped as either deep or superficial to make every possible cross table in which ultrasound tumor location results were presented as a dichotomy. The mean sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the ultrasound to predict the deep location of parotid tumors were 87.5, 82.1, 70.2, 93.6, and 83.8%, respectively. CONCLUSIONS: Stensen's duct on ultrasound can be a useful criterion to determine the location of parotid gland tumor relative to the facial nerve.

Injectable sustained-release poly(lactic-co-glycolic acid) (PLGA) microspheres of exenatide prepared by supercritical fluid extraction of emulsion process based on a design of experiment approach.

This study aimed to develop an improved sustained-release (SR) PLGA microsphere of exenatide using supercritical fluid extraction of emulsions (SFEE). As a translational research, we investigated the effect of various process parameters on the fabrication of exenatide-loaded PLGA microspheres by SFEE (ELPM_SFEE) using the Box-Behnken design (BBD), a design of experiment approach. Further, ELPM obtained under optimized conditions and satisfying all the response criteria were compared with PLGA microspheres prepared using the conventional solvent evaporation (ELPM_SE) method through various solid-state characterizations and in vitro and in vivo evaluations. The four process parameters selected as independent variables were pressure (X 1), temperature (X 2), stirring rate (X 3), and flow ratio (X 4). The effects of these independent variables on five responses, namely the particle size, its distribution (SPAN value), encapsulation efficiency (EE), initial drug burst release (IBR), and residual organic solvent, were evaluated using BBD. Based on the experimental results, a desirable range of combinations of various variables in the SFEE process was determined by graphical optimization. Solid-state characterization and in vitro evaluation revealed that ELPM_SFEE improved properties, including a smaller particle size and SPAN value, higher EE, lower IBR, and lower residual solvent. Furthermore, the pharmacokinetic and pharmacodynamic study results indicated better in vivo efficacy with desirable SR properties, including a reduction in blood glucose levels, weight gain, and food intake, for ELPM_SFEE than those generated using SE. Therefore, the potential drawback of conventional technologies such as the SE for the preparation of injectable SR PLGA microspheres could be improved by optimizing the SFEE process.

Research and Application of Biomass-Based Wood Flame Retardants: A Review.

Wood is widely used as a construction material due to its many advantages, such as good mechanical properties, low production costs, and renewability. However, its flammability limits its use in construction. To solve the problem of wood flammability, the most common method to improve the fire safety of wood is to modify the wood by deep impregnation or surface coating with flame retardants. Therefore, many researchers have found that environmentally friendly and low-cost biomass materials can be used as a source of green flame retardants. Two aspects of biomass-based intumescent flame retardants are summarized in this paper. On the one hand, biomass is used as one of the three sources or as a flame-retardant synergist in combination with other flame retardants, which are called composite biomass intumescent flame retardants. On the other hand, biomass is used alone as a feedstock to produce all-biomass intumescent flame retardants. In addition, the potential of biomass-based materials as an environmentally friendly and low-cost FR source to produce high-performance biomass-based flame retardants with improved technology was also discussed in detail. The development of biomass-based intumescent flame retardants represents a viable and promising approach for the efficient and environmentally friendly production of biomass-based flame retardants.

Research Progress on the Improvement of Flame Retardancy, Hydrophobicity, and Antibacterial Properties of Wood Surfaces.

Wood-based materials are multifunctional green and environmentally friendly natural construction materials, and are widely used in decorative building materials. For this reason, a lot of research has been carried out to develop new and innovative wood surface improvements and make wood more appealing through features such as fire-retardancy, hydrophobicity, and antibacterial properties. To improve the performance of wood, more and more attention is being paid to the functioning of the surface. Understanding and mastering technology to improve the surface functionality of wood opens up new possibilities for developing multifunctional and high-performance materials. Examples of these techniques are ion crosslinking modification and coating modification. Researchers have been trying to make wooden surfaces more practical for the past century. This study has gradually gained popularity in the field of wood material science over the last 10 years. This paper provides an experimental reference for research on wood surface functionalization and summarizes the most current advancements in hydrophobic, antibacterial, and flame-retardant research on wood surfaces.

Improved Aerosolization Stability of Inhalable Tobramycin Powder Formulation by Co-Spray Drying with Colistin.

PURPOSE: Tobramycin shows synergistic antibacterial activity with colistin and can reduce the toxic effects of colistin. The purpose of this study is to prepare pulmonary powder formulations containing both colistin and tobramycin and to assess their in vitro aerosol performance and storage stability. METHODS: The dry powder formulations were manufactured using a lab-scale spray dryer. In vitro aerosol performance was measured using a Next Generation Impactor. The storage stability of the dry powder formulations was measured at 22°C and two relative humidity levels - 20 and 55%. Colistin composition on the particle surface was measured using X-ray photoelectron spectroscopy. RESULTS: Two combination formulations, with 1:1 and 1:5 molar ratios of colistin and tobramycin, showed fine particle fractions (FPF) of 85%, which was significantly higher than that of the spray dried tobramycin (45%). FPF of the tobramycin formulation increased significantly when stored for four weeks at both 20% and 55% RH. In contrast, FPF values of both combination formulations and spray dried colistin remained stable at both humidity levels. Particle surface of each combination was significantly enriched in colistin molecules; 1:5 combination showed 77% by wt. colistin. CONCLUSIONS: The superior aerosol performance and aerosolization stability of 1:1 and 1:5 combination formulations of colistin and tobramycin could be attributed to enrichment of colistin on the co-spray dried particle surface. The observed powder properties may be the result of a surfactant-like assembly of these colistin molecules during spray drying, thus forming a hydrophobic particle surface.

Searching for Invisible Axion Dark Matter with an 18 T Magnet Haloscope.

We report the first search results for axion dark matter using an 18 T high-temperature superconducting magnet haloscope. The scan frequency ranges from 4.7789 to 4.8094 GHz. No significant signal consistent with the Galactic halo dark matter axion is observed. The results set the best upper bound of axion-photon-photon coupling (g_{aγγ}) in the mass ranges of 19.764 to 19.771 µeV (19.863 to 19.890 µeV) at 1.5×|g_{aγγ}^{KSVZ}| (1.7×|g_{aγγ}^{KSVZ}|), and 19.772 to 19.863 µeV at 2.7×|g_{aγγ}^{KSVZ}| with 90% confidence level, respectively. This remarkable sensitivity in the high mass region of dark matter axion is achieved by using the strongest magnetic field among the existing haloscope experiments and realizing a low-noise amplification of microwave signals using a Josephson parametric converter.

Active coating of immediate-release evogliptin tartrate to prepare fixed dose combination tablet with sustained-release metformin HCl.

This study was aimed to develop a fixed dose combination (FDC) tablet containing a low dose of evogliptin tartrate (6.87 mg) for immediate release combined with a high dose (1000 mg) of sustained-release (SR) metformin HCl appropriate for once daily dosing the treatment of type 2 diabetes. To prepare the FDC tablets, an active coating was used in this study, whereby evogliptin tartrate film was layered on a matrix core tablet containing metformin HCl. To overcome the problem caused by a low-dose drug in combination with a relatively large matrix tablet containing high-dose drug, it was also aimed to confirm the formulation and coating operation for satisfactory content uniformity, and to describe the chemical stability during storage of the amorphous active coating layer formulation in relation to molecular mobility. Furthermore, the in vitro release and in vivo pharmacokinetic profiles of metformin HCl and evogliptin tartrate in the FDC active coating tablet were compared to those of the commercially marketed reference drugs, Diabex XR® (Daewoong, Seoul, Korea) containing metformin HCl and Suganon® (Donga ST, Seoul, Korea) containing evogliptin tartrate. In conclusion, the newly developed FDC active coating tablet in this study was confirmed to be bioequivalent to the reference marketed products in beagle dogs, with satisfactory content uniformity and stability.

Gelatin Coating for the Improvement of Stability and Cell Uptake of Hydrophobic Drug-Containing Liposomes.

PURPOSE: Most therapeutic agents have limitations owing to low selectivity and poor solubility, resulting in post-treatment side effects. Therefore, there is a need to improve solubility and develop new formulations to deliver therapeutic agents specifically to the target site. Gelatin is a natural protein that is composed of several amino acids. Previous studies revealed that gelatin contains arginyl-glycyl-aspartic acid (RGD) sequences that become ligands for the integrin receptors expressed on cancer cells. Thus, in this study, we aimed to increase the efficiency of drug delivery into cancer cells by coating drug-encapsulating liposomes with gelatin (gelatin-coated liposomes, GCLs). METHODS: Liposomes were coated with gelatin using electrostatic interaction and covalent bonding. GCLs were compared with PEGylated liposomes in terms of their size, zeta potential, encapsulation efficiency, stability, dissolution profile, and cell uptake. Results: Small-sized and physically stable GCLs were prepared, and they showed high drug-encapsulation efficiency. An in vitro dissolution study showed sustained release depending on the degree of gelatin coating. Cell uptake studies showed that GCLs were superior to PEGylated liposomes in terms of cancer cell-targeting ability. CONCLUSIONS: GCLs can be a novel and promising carrier system for targeted anticancer agent delivery. GCLs, which exhibited various characteristics depending on the coating degree, could be utilized in various ways in future studies.

Formulation, Preparation, Characterization, and Evaluation of Dicarboxylic Ionic Liquid Donepezil Transdermal Patches.

Donepezil (DPZ) is generally administered orally to treat Alzheimer's disease (AD). However, oral administration can cause gastrointestinal side effects. Therefore, to enhance compliance, a new way to deliver DPZ from transdermal patch was developed. Ionic bonds were created by dissolving dicarboxylic acid and DPZ in ethanol, resulting in a stable ionic liquid (IL) state. The synthesized ILs were characterized by differential scanning calorimetry, optical microscope, Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The DPZ ILs were then transformed to a suitable drug-in-adhesive patch for transdermal delivery of DPZ. The novel DPZ ILs patch inhibits crystallization of the IL, indicating coherent design. Moreover, DPZ ILs and DPZ IL patch formulations performed excellent skin permeability compared to that of the DPZ free-base patch in both in vitro and ex vivo skin permeability studies.

Preparation and Characterization of Fenofibrate Microparticles with Surface-Active Additives: Application of a Supercritical Fluid-Assisted Spray-Drying Process.

In this study, supercritical fluid-assisted spray-drying (SA-SD) was applied to achieve the micronization of fenofibrate particles possessing surface-active additives, such as d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), sucrose mono palmitate (Sucroester 15), and polyoxyethylene 52 stearate (Myrj 52), to improve the pharmacokinetic and pharmacodynamic properties of fenofibrate. For comparison, the same formulation was prepared using a spray-drying (SD) process, and then both methods were compared. The SA-SD process resulted in a significantly smaller mean particle size (approximately 2 µm) compared to that of unprocessed fenofibrate (approximately 20 µm) and SD-processed particles (approximately 40 µm). There was no significant difference in the effect on the particle size reduction among the selected surface-active additives. The microcomposite particles prepared with surface-active additives using SA-SD exhibited remarkable enhancement in their dissolution rate due to the synergistic effect of comparably moderate wettability improvement and significant particle size reduction. In contrast, the SD samples with the surface-active additives exhibited a decrease in dissolution rate compared to that of the unprocessed fenofibrate due to the absence of particle size reduction, although wettability was greatly improved. The results of zeta potential and XPS analyses indicated that the surface-active additive coverage on the surface layer of the SD-processed particles with a better wettability was higher than that of the SA-SD-processed composite particles. Additionally, after rapid depletion of hydrophilic additives that were excessively distributed on the surfaces of SD-processed particles, the creation of a surface layer rich in poorly water-soluble fenofibrate resulted in a decrease in the dissolution rate. In contrast, the surface-active molecules were dispersed homogeneously throughout the particle matrix in the SA-SD-processed microparticles. Furthermore, improved pharmacokinetic and pharmacodynamic characteristics were observed for the SA-SD-processed fenofibrate microparticles compared to those for the SD-processed fenofibrate particles. Therefore, the SA-SD process incorporating surface-active additives can efficiently micronize poorly water-soluble drugs and optimize their physicochemical and biopharmaceutical characteristics.

Pharmaceutical Applications of Supercritical Fluid Extraction of Emulsions for Micro-/Nanoparticle Formation.

Micro-/nanoparticle formulations containing drugs with or without various biocompatible excipients are widely used in the pharmaceutical field to improve the physicochemical and clinical properties of the final drug product. Among the various micro-/nanoparticle production technologies, emulsion-based particle formation is the most widely used because of its unique advantages such as uniform generation of spherical small particles and higher encapsulation efficiency (EE). For this emulsion-based micro-/nanoparticle technology, one of the most important factors is the extraction efficiency associated with the fast removal of the organic solvent. In consideration of this, a technology called supercritical fluid extraction of emulsions (SFEE) that uses the unique mass transfer mechanism and solvent power of a supercritical fluid (SCF) has been proposed to overcome the shortcomings of several conventional technologies such as solvent evaporation, extraction, and spray drying. This review article presents the main aspects of SFEE technology for the preparation of micro-/nanoparticles by focusing on its pharmaceutical applications, which have been organized and classified according to several types of drug delivery systems and active pharmaceutical ingredients. It was definitely confirmed that SFEE can be applied in a variety of drugs from water-soluble to poorly water-soluble. In addition, it has advantages such as low organic solvent residual, high EE, desirable release control, better particle size control, and agglomeration prevention through efficient and fast solvent removal compared to conventional micro-/nanoparticle technologies. Therefore, this review will be a good resource for determining the applicability of SFEE to obtain better pharmaceutical quality when researchers in related fields want to select a suitable manufacturing process for preparing desired micro-/nanoparticle drug delivery systems containing their active material.