Characterization of Elastic Polymer-Based Smart Insole and a Simple Foot Plantar Pressure Visualization Method Using 16 Electrodes.

In this paper, we propose a smart insole for inexpensive plantar pressure sensing and a simple visualizing scheme. The insole is composed of two elastomeric layers and two electrode layers where the common top electrode is submerged in the insole. The upper elastomeric layer is non-conductive poly-dimethyl-siloxane (PDMS) and supports plantar pressure buffering and the lower layer is carbon nano-tube (CNT)-dispersed PDMS for pressure sensing through piezo-resistivity. Under the lower sensing layer are 16 bottom electrodes for pressure distribution sensing without cell-to-cell interference. Since no soldering or sewing is needed the smart insole manufacturing processes is simple and cost-effective. The pressure sensitivity and time response of the material was measured and based on the 16 sensing data of the smart insole, we virtually extended the frame size for continuous and smoothed pressure distribution image with the help of a simple pseudo interpolation scheme.

Synthesis of Celecoxib-Eutectic Mixture Particles via Supercritical CO2 Process and Celecoxib Immediate Release Tablet Formulation by Quality by Design Approach.

Significant improvements in the wettability and dissolution rate of celecoxib (CEL), a poorly soluble selective cyclooxygenase-2 (COX-2) inhibitor, have been shown by Huyn et al., 2019 by combining the binary pharmaceutical compositions including CEL and one of the two co-formers, adipic acid (ADI) and saccharin (SAC), into eutectic mixtures (EM). Purpose: In this study, we developed a therapeutic eutectic system for CEL which is a promising approach for oral delivery to enhance bioavailability. CEL EM were synthesized by novel techniques including supercritical CO2 techniques and new tablet formulations were purposed. Methods: CEL EM were synthesized by evaporation crystallization method, spray drying, supercritical fluid (SCF) techniques. The CEL EM particles were then characterized by differential scanning calorimetry, powder X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscope, and particle size analysis. Dissolution studies were carried out. With a quality by design approach, a statistical method through design of experiment and data analysis by JMP® (SAS institute) was applied to CEL EM immediate release tablet formulation development. Results: CEL EM produced by spray drying technique, supercritical fluid (SCF) techniques were identified and characterized. The enhancement of dissolution was observed for SCF processed samples. The design space for CEL-ADI EM IR tablet and control limits for individual parameters were determined.

Factors Affecting Post-Stroke Depression in Acute Ischemic Stroke Patients after 3 Months.

Post-stroke depression (PSD) affects approximately one-third of stroke patients. PSD not only impairs recovery and lowers quality of life, but has also serious neurological consequences, high mortality, and stroke recurrence risks. Studies on PSD-related prognostic factors are still lacking, especially environmental factors. Moreover, relieving factors after PSD in stroke patients has not been reported. This study aimed to investigate (study design 1) risk factors for PSD diagnosis after three months, and (study design 2) related factors for the relieving of early PSD after three months. This retrospective study included 227 patients hospitalized for acute ischemic stroke within three days at Jeonbuk National University Hospital from January to December 2019. The depressive status was assessed using the Hamilton Depression Rating Scale (HDRS) at admission and after three months. Clinical and laboratory data were analyzed for relevant prognostic factors. (Study design 1) HDRS score at admission (adjusted odds ratio (aOR) 1.22, 95% confidence interval (CI) 1.14-1.31; p < 0.001) and hospitalization period (aOR 1.11, 95% CI 1.02-1.20; p = 0.013) were confirmed as prognostic factors of PSD after three months. (Study design 2) The National Institute of Health Stroke Scale (NIHSS) score at discharge (aOR 0.80, 95% CI 0.68-0.94; p = 0.006) and HDRS score at admission (aOR 0.80, 95% CI 0.71-0.89; p < 0.001) were confirmed as prognostic factors of depression improvement after three months. In conclusion, environmental factors such as hospitalization period could be important in managing PSD. Factors related to PSD improvement are expected to be helpful in establishing a strategy for PSD recovery.

Preparation and characterization of glimepiride eutectic mixture with l-arginine for improvement of dissolution rate.

In this study, glimepiride and l-arginine (GA) binary mixtures at various molar ratios were prepared to evaluate whether they could improve the poor water solubility and dissolution characteristics of glimepiride. It was shown that glimepiride and arginine form a eutectic mixture, a type of crystalline solid dispersions, at a 1:1 M ratio and eutectic temperature of 426.9 K using a phase diagram constructed using differential scanning calorimetry (DSC) and thermo-microscopy. The preserved characteristic powder X-ray diffraction (PXRD) patterns and infrared (IR) spectra of each material in those of GA binary mixtures confirmed the formation of eutectic mixture without molecular interaction in solid state. The formation of GA eutectic mixture (GAEM) resulted in the improvement of solubility through pH modification and the intermolecular interaction of glimepiride and l-arginine in aqueous mediums, thereby wettability and dissolution rate of glimepiride were also enhanced. The intermolecular interaction between glimepiride and l-arginine at a 1:1 stoichiometry of the complex in solution state was identified by phase solubility, stoichiometric determination, and solution state nuclear magnetic resonance (NMR) spectroscopy. Specific molecular interactions such as hydrogen bonding and hydrophobic interaction were suggested as main mechanisms of GA complexation in solution. Therefore, this study concludes that the GAEM could be an effective way to improve the solubility and dissolution rate of glimepiride.

Effects of the Immobilization of the Upper Extremities on Spatiotemporal Gait Parameters during Walking in Stroke Patients: A Preliminary Study.

BACKGROUND: The purpose of this study was to investigate the effects of upper extremity immobilization and consequent walking speed on spatiotemporal gait parameters in stroke patients with hemiparesis. METHODS: The following variables were assessed or measured in 29 stroke patients: age, height, weight, disease duration, Korean version of the Mini-Mental State Examination (MMSE-K), Berg balance scale (BBS-K), functional gait assessment (FGA-K), cause of the disease (type of lesion), and hemiparetic side. The measurement of gait was performed using two pressure plates of 1.5 m to create a 3 m walking distance and leaving 1.5 m of extension at both start and end, to ultimately create a 6 m walking distance that the patient could walk through. The following gait patterns were randomly selected based on card draws: self-selected walk speed (SW), self-selected walk speed with immobilized upper extremities (SWI), fast walking (FW), and fast walking with immobilized upper extremities (FWI). Each patient was assessed for four different gait patterns, with three measurements per pattern (12 gait measurements in total). RESULTS: While there were significant differences in the stride length, step width, velocity, and step length of the paretic side between self-selected walk speed (SW) and SWI, FWI did not show significant changes in any of the tested parameters. CONCLUSIONS: Immobilization of the upper extremities may affect walking at self-selected walk speeds. A comprehensive training program including upper extremity movement should be established for gait rehabilitation. Clinical Trial Registration. This trial is registered at http://cris.nih.go.kr/cris.

Melt Amorphisation of Orlistat with Mesoporous Silica Using a Supercritical Carbon Dioxide: Effects of Pressure, Temperature, and Drug Loading Ratio and Comparison with Other Conventional Amorphisation Methods.

The aim of this work was to develop an amorphous orlistat-loaded mesoporus silica formulation using the melt-amorphisation by supercritical fluid (MA-SCF) and to investigate the effects of pressure and temperature on the pharmaceutical properties of the developed formulation. In addition, the effect of orlistat mass ratio to the mesoporus silica was also evaluated. The carbon dioxide was used as a supercritical fluid, and Neusilin®UFL2 was selected as the mesoporous silica. For comparison with conventional amorphisation methods, orlistat formulations were also prepared by solvent evaporation and hot melt methods. Various pharmaceutical evaluations including differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, specific surface area, total pore volume, and content uniformity were performed to characterise the prepared orlistat formulation. The melting point depression and the solubility of orlistat in supercritical carbon dioxide (SC-CO2) were selected for the interpretation of evaluated results in relation to temperature and pressure. The total pore volume of the prepared orlistat-loaded mesoporus silica decreased with an increasing density of SC-CO2 to about 500 g/L at a constant temperature or pressure. From these results, it was suggested that increasing the density of SC-CO2 to about 500 g/L could result in the easier penetration of CO2 into molten orlistat and lower viscosity, hence facilitating the introduction and loading of orlistat into the pores of Neusilin®UFL2. However, when the density of SC-CO2 increased to more than 500 g/L, the total pore volume increased, and this may be due to the release out of orlistat from the pores of Neusilin®UFL2 by the increased orlistat solubility in SC-CO2. Interestingly, as the total pore volume decreased by the filling of the drug, the drug crystallinity decreased; hence, the dissolution rate increased. Furthermore, it was shown that the most desirable mass ratio of Neusilin®UFL2:orlistat for the amorphisation was 1:0.8 at an optimised supercritical condition of 318 K and 10 MPa. Compared with other amorphisation methods, only the sample prepared by the MA-SCF method was in pure amorphous state with the fastest dissolution rate. Therefore, it was concluded that the amorphous orlistat-loaded mesoporus silica prepared using MA-SCF under optimised conditions was more advantageous for enhancing the dissolution rate of orlistat than other conventional amorphisation methods.

Pharmaceutical Characterization and In Vivo Evaluation of Orlistat Formulations Prepared by the Supercritical Melt-Adsorption Method Using Carbon Dioxide: Effects of Mesoporous Silica Type.

Orlistat, an anti-obesity drug, has two critical issues-the first is its low efficacy due to low water solubility and the second is side effects such as oily spotting due to its lipase inhibition. The present study was designed to propose a solution using a formulation with mesoporous silica to simultaneously overcome two issues. Orlistat was loaded onto mesoporous silica by the supercritical melt-adsorption (SCMA) method, using carbon dioxide (CO2). Various types of mesoporous silica were used as adsorbents, and the effects of the pore volume, diameter and particle size of mesoporous silica on the pharmaceutical characteristics were evaluated by various solid-state characterization methods and in vitro and in vivo studies in relation to pharmacological efficacy and the improvement of side effects. The results showed that the pore volume and diameter determine loadable drug amount inside pores and crystallinity. The dissolution was significantly influenced by crystallinity, pore diameter and particle size, and the inhibition of lipase activity was in proportion to the dissolution rate. In vivo studies revealed that the serum triglyceride (TG) concentration was significantly decreased in the group administered amorphous orlistat-loaded Neuisilin®UFL2 with the highest in vitro dissolution rate and lipase activity inhibition in comparison to the commercial product. Furthermore, oily spotting tests in rats revealed that undigested oil was adsorbed onto mesoporous silica after orlistat was released in the gastro-intestinal tract, and it correlated with in vitro result that oil adsorption capacity was dependent on the surface area of empty mesoporous silica. Therefore, it was concluded that mesoporous silica type plays a major role in determining the pharmaceutical characteristics of orlistat formulation prepared using SCMA with CO2 for improving the low solubility and overcoming the side effects.

Characterization and therapeutic efficacy evaluation of glimepiride and L-arginine co-amorphous formulation prepared by supercritical antisolvent process: Influence of molar ratio and preparation methods.

The glimepiride/L-arginine (GA) binary systems were prepared at various molar ratios by using a supercritical antisolvent (SAS) process. For comparison, the GA system was also prepared by physical mixing (PM), melt quenching (MQ), and solvent evaporation (SE) methods. Analyses by DSC and PXRD showed that only the GA binary mixture at 1:1 M ratio prepared by the SAS process was a pure co-amorphous mixture with an excellent content uniformity. On the other hand, GA mixture prepared by PM and SE were not pure co-amorphous systems and contained crystalline eutectic mixture, and MQ method at 170 °C induced the decrease in drug content due to decomposition of glimepiride. The positive deviation of experimentally measured glass transition temperature (Tg) compared to predicted Tg by the Gordon Taylor equation suggests specific molecular interactions between glimepiride and L-arginine in solid-state GA co-amorphous (GACA) mixture. The intermolecular interactions between glimepiride and L-arginine in GACA system were characterized by FT-IR and solid-state NMR analyses. Improved glimepiride dissolution rate of GACA formulation were confirmed using the solubility test, contact angle measurement, and dissolution test. Furthermore, the evaluation of pharmacodynamic hypoglycemic effect demonstrated that GACA prepared by the SAS process significantly improved the therapeutic efficacy of glimepiride.

Preparation, characterization, and evaluation of celecoxib eutectic mixtures with adipic acid/saccharin for improvement of wettability and dissolution rate.

Celecoxib (CEL) is a selective cyclooxygenase-2 (COX-2) inhibitor therapeutically indicated for the treatment of rheumatoid arthritis, osteoarthritis, acute pain, and inflammation. However, its poor solubility and dissolution rate significantly hinders its broader application. In this study, eutectic mixtures, as binary pharmaceutical compositions of CEL with adipic acid (ADI) and saccharin (SAC), were identified through a phase diagram and Tammann's triangle intended to improve the wettability and dissolution rate of poorly water-soluble CEL. The contact angles at 0s in the liquid-solid interface were approximately θs (theta) 79.7 ±â€¯0.50° and 86.65 ±â€¯0.45° for CEL-ADI and CEL-SAC, respectively, which were much lower than the value obtained for CEL (92.05 ±â€¯0.75° θ). Moreover, a comparison of the disk intrinsic dissolution rate and powder dissolution properties demonstrated that eutectic mixtures significantly increased the dissolution rate compared with CEL and physical mixtures. A general relationship was elucidated and indicated that the dissolution rate was increased as the contact angle decreased (correlation coefficient, r = 0.9966 ±â€¯0.0031). Therefore, CEL-ADI and CEL-SAC eutectics may offer a novel formulation strategy to enhance the solubility and oral bioavailability of CEL.