Electrical Characterization of Epoxy Nanocomposite under High DC Voltage.

This work studies the direct current breakdown characteristics of unfilled epoxy and epoxy nonconductive nanocomposites (SiO2,MgO and Al2O3). It also examines the variation of electrical properties in epoxy nanocomposites. The novel aspect of this study is that the samples of Epoxy nanocomposite were exposed to high voltages of up to six kilo volts for three hours using field electron microscopy under high vacuum conditions (10-5 mbar). The current emitted from these samples was measured at three different intervals of time. In addition, the influence of high voltage on the permittivity, loss factor (tan(δ)), and conductivity of the epoxy nanocomposite was studied. This evaluation was conducted before and after applying the voltage at room temperature, The frequency range extends from 10-2-10-7 Hz using the Novo Control Alpha-A analyzer. Current-voltage characterization was performed through field electron microscopy. The samples were characterized by scanning electron microscopy-energy dispersive X-ray spectroscopy and Fourier Transform Infrared Spectroscopy. The unfilled epoxy exhibited structural degradation, resulting in the formation of holes when exposed to high voltages of up to six kilo volts, leading to a reduction in electrical properties. Nevertheless, the addition of nanoparticles shows a significant increase in the operational lifetime of the epoxy nanocomposite. The degree of increase in the lifetime of epoxy composite varied depending on several factors such as the type of NPs introduced and their respective sizes. The epoxy/Al2O3 nanocomposite comparing with epoxy/MgO and epoxy/SiO2 nanocomposite showed elevated resistance to direct current breakdown strength and maintaining its dielectric.

Preparation and in vitro/in vivo characterization of sustained-release ciprofloxacin-carrageenan complex.

The goal of the study was to look into drug-polyelectrolyte complexation between ciprofloxacin (Cipro) and λ-carrageenan (CRG), and to employ the complex as a sustained-release matrix. The maximum binding capacity of the complexation was determined using the dialysis bag method and employed to prepare the complex. In comparison to Cipro, CRG, and their physical mixing, the complex was examined using differential scanning calorimetry, Fourier infrared spectroscopy, powder X-ray diffraction, and scanning electron microscopy. Cipro-CRG matrices, manufactured as direct compression tablets based on the greatest binding capacity, were assessed for swelling, erosion and drug release in 0.1 M HCl, in comparison with those of CRG, Hydroxypropyl methylcellulose (HPMC) and Cipro-HPMC matrices. In vivo absorption study comparing the Cipro-CRG matrix to Cipro immediate-release tablet was also carried out. The greatest binding capacity of Cipro to CRG was 55% (w/w). Multiple interactions, including electrostatic interaction, Vander wall forces, and hydrogen bonding, have been proposed to be involved in complexation with drug amorphization. As a result of the complexation, the swelling and erosion properties of CRG changed, with Cipro-CRG matrix showing substantially less swelling and erosion than Cipro-free CRG matrix. Cipro-CRG matrix exhibited swelling and erosion similar to Cipro-HPMC matrix. However, the former matrix demonstrated Cipro release with significantly less burst impact and a significantly slower release rate. Furthermore, Cipro-CRG matrices in vivo demonstrated slow-prolonged oral drug absorption with consequent significant changes in pharmacokinetic parameters in comparison to those obtained for immediate-release tablets.

Healthy and Pathological Porcine Blood Drop Evaporation: Effect of the Temperature.

This study aims to understand and compare the evaporation dynamics of drops of healthy and pathological porcine blood (glomerulonephritis disease) evaporated on hydrophilic glass substrates at different surface temperatures (Ts): 23, 37, 60, and 90 °C. Subsequently, the different induced phenomena are characterized and described. Additionally, drops of water were evaporated at these four surface temperatures to better understand the difference between healthy and pathological porcine blood. Statistical studies were performed to analyze the evaporation rate, the maximum and average values of Marangoni numbers (Ma), and the evaporated specific time. The statistical tests showed significant differences in these parameters between healthy and pathological blood for each surface temperature. The mean and the maximum of the Ma increase with the increase in Ts caused by the increase in the temperature differences between the edge and the center of the drop. When comparing healthy and diseased blood, the Ma maximum and mean of healthy blood were higher than those of diseased blood for all Ts. Besides, this study emphasizes the influence of temperature on blood evaporation and the pattern caused by the Marangoni effect. These results demonstrate that differences between the two blood types are related to the disease and pave the way to developing a new methodology for medical decision-making.

Effect of temperature on evaporation dynamics of sheep's blood droplets and topographic analysis of induced patterns.

To characterize various induced phenomena and the blood of healthy sheep using several parameters, the evaporation dynamics of 72 drops of sheep blood evaporated at several temperatures: 23, 37, 60, and 90 °C on glass hydrophilic substrates were studied. This allows the prediction of the sheep blood pattern, knowing the surface temperature and vice versa. To determine the variation in the Marangoni number between the center and the triple line, an infrared thermography method was used to measure the temperature variation along the surface of the drop. Simultaneously, a high-performance camera was used to measure the variation in the height of the drop during the evaporation using a superior algorithm software for image analysis, drop shape analyzer, under controlled conditions (Humidity = 40%, Tatm = 23 °C). The study of the evaporation dynamics and pattern formation shows the effect of temperature on the flow circulation inside the drop, resulting in the final deposit. The results showed two categories corresponding to two different evaporation phenomena induced by the thermal Marangoni effect. Furthermore, to transform the induced pattern of sheep blood evaporation into a 3D image, a topographic study was performed using a highly accurate, fast, and flexible optical 3D measurement system. The topographic parameters were subsequently extracted from these 3D images. The statistical study showed a good correlation between the topographic parameters and the surface temperature, and a significant difference between each temperature group for each parameter.

Balanced Scorecard-Based Hospital Performance Measurement Framework: A Performance Construct Development Approach.

Introduction Despite the critical importance of hospital performance measurement, empirically validated hospital performance frameworks lack. The balanced scorecard is considered one of the most influential contributions in the performance measurement literature. Since the introduction of the balanced scorecard in the early 90s, many scholars have used a balanced scorecard to enable hospital performance measurement and improvement. Therefore, this study aimed to construct and validate a balanced scorecard-based hospital performance framework. Additional to the original four perspectives, the quality of care is added as a perspective for the balanced hospital scorecard. It reflects one of the key strategic objectives in any healthcare organization. Methods The study adopted a two-phase model to validate the framework empirically. The first is the exploratory phase, where feedback from academicians and professionals helped finalize the framework in the form of scale. In the second phase, the scale was tested for dimensionality, reliability, and validity. Results A total of 200 (81 responded, RR= 40%) senior managers working in Hamad Medical Corporation (HMC), the largest healthcare provider in Qatar, were surveyed. The content, convergent, and discriminant validities were established. The study conducted composite reliability and Cronbach's alpha tests for the reliability, and all variables were found to have alpha and composite reliability higher than 0.7. Conclusion The findings suggest that senior managers in HMC make a meaningful distinction between the five attributes of hospital performance. Findings, contributions, limitations, directions for future research, and managerial implications are all discussed.

Interfacial viscoelastic moduli in a weak gel.

HYPOTHESIS: The measurement of interfacial viscoelastic moduli provides information on the ability of surface-active agents to texture the interface. However, the contribution of the bulk rheology cannot be ignored in particular when the continuous phase exhibits a gel-like behavior, even with low modulus. EXPERIMENTS: Between 2 and 6 g/L, κ-carrageenan aqueous solutions have no significant activities at interfaces. At low concentrations or high temperatures, they behave like Newtonian liquids. Upon heating or cooling, a reversible liquid/gel transition appears with a hysteresis where the rheological behavior can be easily modulated by adjusting κ-carrageenan concentration. The frequency dependence of bulk and interfacial viscoelastic moduli are determined using a conventional shear rheometer and a drop tensiometer with a polyisobutene oil, respectively. FINDINGS: The effect of concentration and temperature is analyzed and the frequency dependence of interfacial moduli is correlated with those of the bulk. In presence of a gelled κ-carrageenan solutions, an elastic behavior of the interface appears and strengthens as the elastic modulus of the suspended phase is high. It turns out that the oscillating pendant drop method could be a sensitive indicator of the presence of very weak gels, even hardly detected by a shear classical rheometry.

Ambroxol Hydrochloride Loaded Gastro-Retentive Nanosuspension Gels Potentiate Anticancer Activity in Lung Cancer (A549) Cells.

This study aimed to develop gastro-retentive sustained-release ambroxol (ABX) nanosuspensions utilizing ambroxol-kappa-carrageenan (ABX-CRGK) complexation formulations. The complex was characterized by differential scanning calorimetry, powder x-ray diffractometer, and scanning electron microscopy. The prepared co-precipitate complex was used for the development of the sustained-release formulation to overcome the high metabolic and poor solubility problems associated with ABX. Furthermore, the co-precipitate complex was formulated as a suspension in an aqueous floating gel-forming vehicle of sodium alginate with chitosan, which might be beneficial for targeting the stomach as a good absorption site for ABX. The suspension exhibited rapid floating gel behaviour for more than 8 h, thus confirming the gastro-retentive effects. Particle size analysis revealed that the optimum nanosuspension (ABX-NS) had a mean particle size of 332.3 nm. Afterward, the ABX released by the nanoparticles would be distributed to the pulmonary tissue as previously described. Based on extensive pulmonary distribution, the developed nanosuspension-released ABX nanoparticles showed significant cytotoxic enhancement compared to free ABX in A549 lung cancer cells. However, a significant loss of mitochondrial membrane potential (MMP) also occurred. The level of caspase-3 was the highest in the ABX-NS-released particle-treated samples, with a value of 416.6 ± 9.11 pg/mL. Meanwhile, the levels of nuclear factor kappa beta, interleukins 6 and 1 beta, and tumour necrosis alpha (NF-kB, IL-6, IL-1ß, and TNF-α, respectively) were lower for ABX-NS compared to free ABX (p < 0.05). In caspase-3, Bax, and p53, levels significantly increased in the presence of ABX-NS compared to free ABX. Overall, ABX-NS produced an enhancement of the anticancer effects of ABX on the A549 cells, and the developed sustained-release gel was successful in providing a gastro-retentive effect.

Estimation of endothelial shear stress in atherosclerotic lesions detected by intravascular ultrasound using computational fluid dynamics from coronary CT scans with a pulsatile blood flow and an individualized blood viscosity.

INTRODUCTION: Endothelial shear stress (ESS) is a local hemodynamic factor that is dependent on vessel geometry and influences the process of atherogenesis. As in vivo measurements of ESS are not possible, it must be calculated using computational fluid dynamics (CFD). In this feasibility study we explore CFD-models generated from coronary CT-angiography (CCTA) using an individualised blood viscosity and a pulsatile flow profile derived from in vivo measurements. MATERIALS AND METHODS: We retrospectively recruited 25 consecutive patients who received a CCTA followed by a coronary angiography including intravascular ultrasound (IVUS) and generated 3D models of the coronary arteries from the CT-datasets. We then performed CFD-simulations on these models. Hemodynamically non-relevant stenosis were identified in IVUS. They were isolated in the CFD-model and separated longitudinally into a half with atherosclerotic lesion (AL) and one without (NAL). ESS was measured and compared for both halves. RESULTS: After excluding vessels with no IVUS data or relevant stenosis we isolated 31 hemodynamically non-relevant excentric AL from a total of 14 vessels. AL segments showed consistently significantly lower ESS when compared to their corresponding NAL segments when regarding minimum (0.9 Pa, CI [0.6, 1.2] vs. 1.3 Pa, CI [0.9, 1.8]; p = 0.004), mean (5.0 Pa, CI [3.4, 6.0] vs. 6.7 Pa, CI [5.5, 8.4]; p = 0.008) and maximum ESS values (12.4 Pa, CI [8.6, 14.6] vs. 19.6 Pa, CI [12.4, 21.0]; p = 0.005). Qualitatively ESS was lower on the inside of bifurcations and curvatures. CONCLUSION: CFD simulations of coronary arteries from CCTA with an individualised flow profile and blood viscosity are feasible and could provide further prognostic information and a better risk stratification in coronary artery disease. Further prospective studies are needed to investigate this claim.

Preparedness of Frontline Doctors in Jordan Healthcare Facilities to COVID-19 Outbreak.

The number of COVID-19 (Coronavirus Disease of 2019) cases in Jordan is rising rapidly. A serious threat to the healthcare system appears on the horizon. Our study aims to evaluate preparedness of Jordanian frontline doctors to the worsening scenario. It has a questionnaire-based cross-sectional structure. The questionnaire was designed to evaluate preparedness according to knowledge about virus transmission and protective measures, adherence to protection guidelines, and psychological impacts affecting doctors. Institutional factors affecting doctors' readiness like adopting approach protocols and making protection equipment available were investigated; 308 doctors from different healthcare facilities participated (response rate: 53.9%). Approximately 25% of doctors (n = 77) previously took care of COVID-19 patients, and 173 (56.2%) have institutional COVID-19 approach protocols. Only 57 doctors (18.5%) reported all PPE (Personal Protective Equipment) available. The self-reported score of preparedness to deal with COVID-19 patients was 4.9 ± 2.4. Doctors having institutional protocols for dealing with COVID-19 cases and those with sustained availability of PPE reported higher scores of preparedness (5.5 ± 2.3 and 6.2 ± 2.1 with p < 0.001, respectively). Correlations with knowledge score, adherence to PPE score, and psychological impacts were investigated. The study revealed multiple challenges and insufficiencies that can affect frontline doctors' preparedness. Policy makers are urged to take these findings into consideration and to act promptly.

Development and characterization of novel ambroxol sustained-release oral suspensions based on drug-polymeric complexation and polymeric raft formation.

The aim was to develop sustained-release aqueous suspensions of ambroxol utilizing drug-polymer complexation and raft-forming formulations. Ambroxol-carrageenan (ABX-CRG) complexation was studied for the optimum binding capacity, which was used to prepare the complex by kneading and coprecipitation. The prepared complex was characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffractometry. The complex was formulated as suspensions in aqueous raft-forming vehicle of sodium alginate (NA) and calcium carbonate (CC). The suspensions differed in the molecular weight and concentration of NA, in addition to CC level and inclusion of CRG in excess of drug-polymer complexation. In 0.1 M HCl as simulated gastric fluid, the suspensions were observed for their ability to form rafts and studied for drug-release. The optimum sustained-release, raft forming and pourable formulation using high molecular weight NA, NA concentration of 18 mg/ml and CC concentration of 9 mg/ml was reached. Another optimum suspension was obtained by replacement of CC with excess CRG. However, pH dissolution profiles of the optimum suspensions revealed less pH sensitivity of the release consequent to this replacement as well as more stable ABX release upon aging. Relative to Gaviscon liquid, the optimum suspensions formed rafts of similar strength and higher resilience.

Porto-Rex Shunt for Left Portal Vein Reconstruction During Right Extended Hepatectomy for Advanced Extrahepatic Biliary Cancer.

Resection offers the only chance of long-term survival or cure for perihilar cancer, provided R0 resection is achieved with margin-negative status of the remnant liver, bile duct, proximal hepatic artery, and portal vein. End-to-end anastomosis of the portal trunk to the left portal branch is the conventional portal reconstruction in cases of right extended hepatectomy requiring resection of the portal vein bifurcation. This mandatory reconstruction may be challenging due to (1) vessel incongruence, (2) fragility of the left portal branch wall, and more importantly, and (3) the divergent orientation of the two vessels exposing to vascular twisting/kinking. We report here the first two cases of porto-Rex shunt, between the portal vein trunk and the left portal vein in the umbilical fissure during right extended hepatectomy for advanced extrahepatic biliary cancer: one following failed conventional portal reconstruction and one to achieve macroscopically complete resection.

In Vitro and In Vivo Evaluation of Casein as a Drug Carrier for Enzymatically Triggered Dissolution Enhancement from Solid Dispersions.

Due to its unique properties, such as biodegradability, biocompatibility, high amphiphilic property, and micelle formation, casein (CS) has been increasingly studied for drug delivery. We used CS as a drug carrier in solid dispersions (SDs) and evaluated the effect of its degradation by trypsin on drug dissolution from the dispersions. SDs of CS and mefenamic acid (MA) were prepared by physical mixing, kneading, and coprecipitation methods. In comparison to pure MA, the dispersions were evaluated for drug-protein interaction, loss of drug crystalinity, and drug morphology by differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy, and scanning electron microscopy. Drug dissolution from the dispersions was evaluated in simulated intestinal fluid as enzyme free and trypsin-enriched media. Furthermore, in vivo drug absorption of MA from CS-MA coprecipitate was evaluated in rats, in comparison with a reference SD of polyethylene glycol and MA (PEG-MA SD). Relative to other CS preparations, CS-MA coprecipitate showed the highest loss of drug crystallinity, drug micronization, and CS-MA interaction. CS remarkably enhanced the dissolution rate and extent of MA from the physical and kneaded mixtures. However, the highest dissolution enhancement was obtained when MA was coprecipitated with CS. Trypsin that can hydrolyze CS during dissolution resulted in further enhancement of MA dissolution from the physical and kneaded mixtures. However, a corresponding retardation effect was obtained for the coprecipitate. In correlation with in vitro drug release, CS-MA coprecipitate also showed significantly higher MA bioavailability in rats than PEG-MA SD.

Preparation and Evaluation of Newly Developed Chitosan Salt Coating Dispersions for Colon Delivery without Requiring Overcoating.

Although chitosan (CS) has been recognized as a good material for colon-specific drug delivery systems, an overcoating with an enteric coating polymer on the surface of CS is absolutely necessary because CS is soluble in acidic conditions before reaching the colon. In the present study, to improve its stability in the presence of acid, a newly developed CS-laurate (CS-LA) material was evaluated as a coating dispersion for the development of colon-specific drug delivery systems. Two types of CS with different molecular weights, CS250 and CS600, were used to prepare CS-LA films by the casting method. The CS250-LA films had smooth surfaces, whereas the surfaces of the CS600-LA films were rough, indicating that the CS250-LA dispersion could form a denser film than CS600-LA. Both of these CS-LA films maintained a constant shape over 22 h in a pH 1.2 HCl/NaCl buffer, where the corresponding CS films rapidly disintegrated. In addition, the CS250-LA film showed specific colon degradability in a pH 6.0 phosphate buffered solution containing 1.0% (w/v) ß-glucosidase. As a result of tensile strength and elongation at the break, both CS-LA films were found to have flexible film properties. Finally, the release of acetaminophen from disks coated with CS250-LA dispersions was significantly suppressed in fluids at pH 1.2 and 6.8, whereas disks coated with CS solution rapidly released the drug in pH 1.2 fluids. Taken together, this study shows that LA modification could be a useful approach in preparing CS films with acid stability and colonic degradability properties without requiring overcoating.

A newly developed lubricant, chitosan laurate, in the manufacture of acetaminophen tablets.

To study the usefulness of chitosan laurate (CS-LA), a newly developed chitosan salt, as a lubricant, lubrication properties such as the pressure transmission ratio and ejection force were determined at different concentrations of CS-LA in tableting. In addition, tablet properties such as the tensile strength, disintegration time, and dissolution behavior, were also determined. When CS-LA was mixed at concentrations of 0.1%-3.0%, the pressure transmission ratio was increased in a concentration-dependent manner, and the value at a CS-LA concentration of 3% was equal to that of magnesium stearate (Mg-St), a widely used lubricant. Additionally, a reduction in the ejection force was observed at a concentration from 1%, proving that CS-LA has good lubrication performance. A prolonged disintegration time and decreased tensile strength, which are known disadvantages of Mg-St, were not observed with CS-LA. Furthermore, with CS-LA, retardation of dissolution of the drug from the tablets was not observed. Conjugation of CS with LA was found to be quite important for both lubricant and tablet properties. In conclusion, CS-LA should be useful as an alternative lubricant to Mg-St.

Coronary computed tomography angiography based assessment of endothelial shear stress and its association with atherosclerotic plaque distribution in-vivo.

PURPOSE: The relationship between low endothelial shear stress (ESS) and coronary atherosclerosis is well established. ESS assessment so far depended on invasive procedures. The aim of this study was to demonstrate the relationship between ESS and coronary atherosclerosis by using non-invasive coronary computed tomography angiography (CTA) for computational fluid dynamics (CFD) simulations. METHODS: A total number of 7 consecutive patients with suspected coronary artery disease who received CTA and invasive angiography with IVUS analysis were included in this study. CTA examinations were performed using a dual-source scanner. These datasets were used to build a 3D mesh model. CFD calculations were performed using a validated CFD solver. The presence of plaque was assumed if the thickness of the intima-media complex exceeded 0.3 mm in IVUS. Plaque composition was derived by IVUS radiofrequency data analysis. RESULTS: Plaque was present in 32.1% of all analyzed cross-sections. Plaque prevalence was highest in areas of low ESS (49.6%) and high ESS (34.8%). In parts exposed to intermediate-low and intermediate-high ESS few plaques were found (20.0% and 24.0%) (p<0.001). Wall thickness was closely associated with local ESS. Intima-media thickness was 0.43±0.34 mm in low and 0.38±0.32 mm in high ESS segments. It was significantly lower when the arterial wall was exposed to intermediate ESS (0.25±0.18 mm and 0.28 ± 0.20 mm) (p<0.001). Fibrofatty tissue was predominately found in areas exposed to low ESS (p≤0.023). CONCLUSIONS: In this study a close association of atherosclerotic plaque distribution and ESS pattern could be demonstrated in-vivo. Adding CFD analysis to coronary CTA offers the possibility to gather morphologic and physiologic data within one non-invasive examination.

The synthesis and characterization of fatty acid salts of chitosan as novel matrices for prolonged intragastric drug delivery.

The aim of this study was to prepare fatty acid salts of chitosan (CS) and to evaluate the salts as matrices for sustained drug release and prolonged gastric retention. CS-laurate and CS-palmitate were formed by mixing saturated CS solution and aqueous solutions of sodium laurate and sodium palmitate, respectively, and collected by centrifugation. They were characterized using Fourier-transform infrared spectroscopy and differential scanning calorimetry. Different matrices as effervescent tablets were prepared using each of these CS-salts, CS and the corresponding physical mixtures of CS and the fatty acids. Sodium bicarbonate as an effervescent agent and ranitidine HCl as a model drug were incorporated into these matrices. In vitro buoyancy and drug dissolution were studied for the matrices in 0.1 M HCl. Tablets with fatty acid salts of CS showed both rapid and prolonged buoyancy (> 8 h). Comparatively, CS tablets exhibited a short floatation period (< 2 h) and tablets were completely disintegrated within 1 h of soaking. In addition, slow and prolonged drug release was achieved from tablets of fatty acid salts of CS with average drug release of 80.1 and 71.8% for CS-laurate and CS-palmitate, respectively. Rapid drug release (> 80% at 1 h) was exhibited by tablets with CS or the physical mixtures.

Prolonged intragastric drug delivery mediated by Eudragit® E-carrageenan polyelectrolyte matrix tablets.

Interpolyelectrolyte (IPE) complexation between carrageenan (CG) and Eudragit E (EE) was studied in 0.1 M HCl and was used to develop floating matrix tablets aimed to prolong gastric-residence time and sustain delivery of the loaded drug. The optimum EE/CG IPE complexation weight ratio (0.6) was determined in 0.1 M HCl using apparent viscosity measurements. The IPE complex was characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. Metronidazole matrix tablets were prepared by direct compression using EE, CG, or hybrid EE/CG with ratio optimal for IPE complexation. Corresponding effervescent tablets were prepared by including Na bicarbonate as an effervescent agent. Tablets were evaluated for in vitro buoyancy and drug release in 0.1 M HCl. Both CG and EE-CG effervescent matrices (1:2 drug to polymer weight ratio, 60 mg Na bicarbonate) achieved fast and prolonged floating with floating lag times less than 30 s and floating duration of more than 10 h. The corresponding EE effervescent matrices showed delayed floating and rapid drug release, and completely dissolved after 3 h of dissolution. CG matrices showed an initial burst drug release (48.3±5.0% at 1 h) followed by slow drug release over 8 h. EE-CG matrices exhibited sustained drug release in almost zero-order manner for 10 h (68.2±6.6%). The dissolution data of these matrices were fitted to different dissolution models. It was found that drug release followed zero-order kinetics and was controlled by the superposition of the diffusion and erosion.

Floating and sustained-release characteristics of effervescent tablets prepared with a mixed matrix of Eudragit L-100-55 and Eudragit E PO.

The aim of this study was to evaluate the influence of Na-bicarbonate as an effervescent agent on the floating and sustained-release characteristics in 0.1 M HCl of tablets made of Eudragit E PO (EE) and/or Eudragit L-100-55 (EL) as matrix formers at different EE:EL weight ratios: 0:100, 25:75, 50:50, 75:25, and 100:0. The tablets were made by direct compression utilizing metronidazole as a model drug. Effervescent tablets with 50EE/50EL (w/w) showed the best floating and sustained drug release properties in the dissolution medium. The corresponding noneffervescent tablets were nonfloating and showed significantly faster drug release. Effervescent tablets with single polymers showed an immediate drug release pattern. These results were explained by Fourier-transform infrared spectroscopy and elemental analysis, which showed strong evidence of interpolyelectrolyte complexation between EE and EL when they were exposed to 0.1 M HCl as an effervescent hybrid matrix, but not as a noneffervescent hybrid matrix. The role of Na-bicarbonate in allowing EE-EL complexation during dissolution was explained as due to raising the pH around EL particles for sufficient polymer ionization and ionic-interaction with the ionized EE.

Diclofenac-bismuth complex: synthesis, physicochemical, and biological evaluation.

Diclofenac-bismuth complexation was attempted by mixing diclofenac sodium (Na) and bismuth-subcitrate aqueous solutions at diclofenac:bismuth molar ratio of 3:1. A solid precipitate was obtained and isolated. The precipitate was characterized for stoichiometric ratio of diclofenac-bismuth complexation using capillary electrophoresis, which showed 1:1 complexation. In addition, nuclear magnetic resonance and Fourier transform infrared analysis were performed for the isolated solid complex and indicated that bismuth was in coordinate bond formation with the carboxylate group of diclofenac. In comparison with diclofenac Na powder, the complex was evaluated as an aqueous suspension for in vitro drug dissolution. The complex exhibited a faster dissolution rate than and similar dissolution extent as diclofenac Na. In comparison with an aqueous solution of diclofenac Na and an aqueous suspension of physical mixture of diclofenac acid (suspended) and bismuth-subcitrate (dissolved), the aqueous complex suspension was evaluated for ulcerogenic effect in rats upon oral administration. The complex led to more gastric ulceration than diclofenac Na, which was not in accordance with the antiulcer properties of bismuth. This antiulcer effect was shown as the physical mixture administration was accompanied with lower gastric ulceration than diclofenac Na administration. These gastric ulceration results were explained in terms of the difference in particle size between solid diclofenac acid formed as a result of the complex breakdown in an acidic medium (0.1 M HCl to simulate the gastric fluid) and that formed as a result of diclofenac Na neutralization. Diclofenac acid particles formed from the complex breakdown were of average size, three times smaller of those formed as a result of diclofenac Na protonation. This difference in particle size was correlated with the higher gastric ulceration associated with the complex than with diclofenac Na in terms of higher coverage of the gastric mucosa with diclofenac, and consequently, higher local ulceration.

Sodium mefenamate as a solution for the formulation and dissolution problems of mefenamic acid.

Sodium salt formation of mefenamic acid (MA) was studied as a way to solve the formulation and dissolution problems of MA. For this purpose, sodium salt of mefenamic acid (Na-MA) was prepared by reacting MA powder with equimolar sodium hydroxide in an aqueous phase, and consequently, Na-MA solution was obtained. The resultant solution was lyophilized and Na-MA powder was collected. The salt formation was confirmed by the results of fourier transformation-infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies on Na-MA powder in comparison to MA powder. Na-MA powder was assessed for direct compressibility, in comparison to MA powder, when formulated as a mixture with minimum amount of Avicel((R)) pH 101 and then compressed into tablets using a hydraulic tablet press. Na-MA tablets exhibited satisfactory hardness and friability, and did not show capping or lamination. On the other hand, some MA tablets showed capping or lamination upon compression and all the tested MA tablets for friability capped. Na-MA tablets were also studied for drug dissolution, in comparison to MA tablets, in water, a pH 7.4 phosphate buffer, and a pH 7.4 phosphate buffer after soaking in 0.1 m HCl. Under these different dissolution conditions, Na-MA tablets showed much higher dissolution rate and extent than MA tablets. The results of the study suggested that Na-MA can be considered as a solution form for the formulation and dissolution problems of MA.