A Methodological Approach for Motor Selection in Dental Impression Material Dispensers Using Experimental and Image Analysis Techniques.

This study presents a methodology to prevent the overdesign of electric dispensers for dental impression materials by analyzing the necessary load and determining the appropriate pressurization speed and drive motor capacity. We derived an equation to calculate the required torque and rotational speed of the motor based on the extrusion load and the speed of the impression material. A specialized load measurement system was developed to measure the load necessary to extrude the impression material. Through experiments and image processing, we measured the radius of curvature of the trajectory of the impression material and correlated it with the pressurization speed. Techniques such as position coordinate plotting, curve fitting, and circle fitting were employed to determine the pressurization speed that aligns with the manufacturer's recommended curvature radius. These findings led to a substantial decrease in the necessary motor torque and rotational speed compared with the current standards. This research provides a systematic approach to sizing drive motors using extrusion load and pressurization speed, aiming to reduce overdesign, power consumption, and the weight and size of the motor and battery, thereby contributing to the development of more efficient and compact dental impression material dispensers.

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.

Expression Patterns of PAK4 and PHF8 Are Associated with the Survival of Gallbladder Carcinoma Patients.

BACKGROUND: PAK4 and PHF8 are involved in cancer progression and are under evaluation as targets for cancer therapy. However, despite extensive studies in human cancers, there are limited reports on the roles of PAK4 and PHF8 in gallbladder cancers. METHODS: Immunohistochemical expression of PAK4 and PHF8 and their prognostic significance were evaluated in 148 human gallbladder carcinomas. RESULTS: PAK4 expression was significantly associated with PHF8 expression in gallbladder carcinomas. Positive expression of nuclear PAK4, cytoplasmic PAK4, nuclear PHF8, and cytoplasmic PHF8 were significantly associated with shorter overall survival and relapse-free survival in univariate analysis. Multivariate analysis showed that nuclear PAK4 expression and nuclear PHF8 expression were independent predictors of overall survival and relapse-free survival in gallbladder carcinomas. Furthermore, coexpression of nuclear PAK4 and nuclear PHF8 predicted shorter overall survival (p < 0.001) and relapse-free survival (p < 0.001) of gallbladder carcinoma in multivariate analysis. CONCLUSIONS: This study suggests that the individual and coexpression patterns of PAK4 and PHF8 as the prognostic indicators for gallbladder carcinoma patients.

Pure Trans-Resveratrol Nanoparticles Prepared by A Supercritical Antisolvent Process Using Alcohol and Dichloromethane Mixtures: Effect of Particle Size on Dissolution and Bioavailability in Rats.

The aim of this study was to prepare pure trans-resveratrol nanoparticles without additives (surfactants, polymers, and sugars) using a supercritical antisolvent (SAS) process with alcohol (methanol or ethanol) and dichloromethane mixtures. In addition, in order to investigate the effect of particle size on the dissolution and oral bioavailability of the trans-resveratrol, two microparticles with different sizes (1.94 µm and 18.75 µm) were prepared using two different milling processes, and compared to trans-resveratrol nanoparticles prepared by the SAS process. The solid-state properties of pure trans-resveratrol particles were characterized. By increasing the percentage of dichloromethane in the solvent mixtures, the mean particle size of trans-resveratrol was decreased, whereas its specific surface area was increased. The particle size could thus be controlled by solvent composition. Trans-resveratrol nanoparticle with a mean particle size of 0.17 µm was prepared by the SAS process using the ethanol/dichloromethane mixture at a ratio of 25/75 (w/w). The in vitro dissolution rate of trans-resveratrol in fasted state-simulated gastric fluid was significantly improved by the reduction of particle size, resulting in enhanced oral bioavailability in rats. The absolute bioavailability of trans-resveratrol nanoparticles was 25.2%. The maximum plasma concentration values were well correlated with the in vitro dissolution rate. These findings clearly indicate that the oral bioavailability of trans-resveratrol can be enhanced by preparing pure trans-resveratrol nanoparticles without additives (surfactants, polymers, and sugars) by the SAS process. These pure trans-resveratrol nanoparticles can be applied as an active ingredient for the development of health supplements, pharmaceutical products, and cosmetic products.

Preparation and Evaluation of Resveratrol-Loaded Composite Nanoparticles Using a Supercritical Fluid Technology for Enhanced Oral and Skin Delivery.

We created composite nanoparticles containing hydrophilic additives using a supercritical antisolvent (SAS) process to increase the solubility and dissolution properties of trans-resveratrol for application in oral and skin delivery. Physicochemical properties of trans-resveratrol-loaded composite nanoparticles were characterized. In addition, an in vitro dissolution-permeation study, an in vivo pharmacokinetic study in rats, and an ex vivo skin permeation study in rats were performed. The mean particle size of all the composite nanoparticles produced was less than 300 nm. Compared to micronized trans-resveratrol, the trans-resveratrol/hydroxylpropylmethyl cellulose (HPMC)/poloxamer 407 (1:4:1) nanoparticles with the highest flux (0.792 µg/min/cm2) exhibited rapid absorption and showed significantly higher exposure 4 h after oral administration. Good correlations were observed between in vitro flux and in vivo pharmacokinetic data. The increased solubility and flux of trans-resveratrol generated by the HPMC/surfactant nanoparticles increased the driving force on the gastrointestinal epithelial membrane and rat skin, resulting in enhanced oral and skin delivery of trans-resveratrol. HPMC/surfactant nanoparticles produced by an SAS process are, thus, a promising formulation method for trans-resveratrol for healthcare products (owing to their enhanced absorption via oral administration) and for skin application with cosmetic products.

Development of a Resveratrol Nanosuspension Using the Antisolvent Precipitation Method without Solvent Removal, Based on a Quality by Design (QbD) Approach.

The purpose of this study was to develop a resveratrol nanosuspension with enhanced oral bioavailability, based on an understanding of the formulation and process parameters of nanosuspensions and using a quality by design (QbD) approach. Particularly, the antisolvent method, which requires no solvent removal and no heating, is newly applied to prepare resveratrol nanosuspension. To ensure the quality of the resveratrol nanosuspensions, a quality target product profile (QTPP) was defined. The particle size (z-average, d90), zeta potential, and drug content parameters affecting the QTPP were selected as critical quality attributes (CQAs). The optimum composition obtained using a 3-factor, 3-level Box-Behnken design was as follows: polyvinylpyrrolidone vinyl acetate (10 mg/mL), polyvinylpyrrolidone K12 (5 mg/mL), sodium lauryl sulfate (1 mg/mL), and diethylene glycol monoethyl ether (DEGEE, 5% v/v) at a resveratrol concentration of 5 mg/mL. The initial particle size (z-average) was 46.3 nm and the zeta potential was -38.02 mV. The robustness of the antisolvent process using the optimized composition conditions was ensured by a full factorial design. The dissolution rate of the optimized resveratrol nanosuspension was significantly greater than that of the resveratrol raw material. An in vivo pharmacokinetic study in rats showed that the area under the plasma concentration versus time curve (AUC0-12h) and the maximum plasma concentration (Cmax) respectively, than those of the resveratrol raw material. Therefore, the prepara values of the resveratrol nanosuspension were approximately 1.6- and 5.7-fold higher,tion of a resveratrol nanosuspension using the QbD approach may be an effective strategy for the development of a new dosage form of resveratrol, with enhanced oral bioavailability.

Development of an integrated process to produce d-mannose and bioethanol from coffee residue waste.

A novel, integrated process for economical high-yield production of d-mannose and ethanol from coffee residue waste (CRW), which is abundant and widely available, was reported. The process involves pretreatment, enzymatic hydrolysis, fermentation, color removal, and pervaporation, which can be performed using environmentally friendly technologies. The CRW was pretreated with ethanol at high temperature and then hydrolyzed with enzymes produced in-house to yield sugars. Key points of the process are: manipulations of the fermentation step that allowing bioethanol-producing yeasts to use almost glucose and galactose to produce ethanol, while retaining large amounts of d-mannose in the fermented broth; removal of colored compounds and other components from the fermented broth; and separation of ethanol and d-mannose through pervaporation. Under optimized conditions, approximately 15.7g dry weight (DW) of d-mannose (approximately 46% of the mannose) and approximately 11.3g DW of ethanol from 150g DW of ethanol-pretreated CRW, were recovered.