A Novel Polymeric Membrane Sensor for Chlorhexidine Determination.

In the present work, potentiometric sensors with polymer membranes used for chlorhexidine (CHXD) determination were developed. The polymer membranes were plasticized with bis(2-ethylheksyl)sebacate (DOS) or 2-nitrophenyloctyl ether (o-NPOE). The active compounds used in the membrane were cyclodextrins, crown ethers, and ion exchangers. The best-constructed electrode was based on neutral heptakis(2,3,6-tri-O-benzoyl)-ß-cyclodextrin with lipophilic salt (KTpClBP)-potassium tetrakis(4-chlorophenyl) borate-dissolved in plasticizer, DOS. The presented electrode is characterized by an average cationic slope of 30.9 ± 2.9 mV decade-1 within a linear range of 1 × 10-6 to 1 × 10-3 mol × L-1, while the value of the correlation coefficient is 0.9970 ± 0.0026. The response time was about 5 s when increasing the sample concentration and about 10 s when diluting the sample. The electrode potential is independent of the pH within a range of 4.0-9.5. The polymeric membrane sensor was successfully applied for assays of chlorhexidine digluconate in pure samples and pharmaceutical samples. The relative error from three replicate measurements was determined to be 1.1%. and the accuracy was RSD = 0.3-1.1%.

The Use of Calcium Phosphate-Based Starter Pellets for the Preparation of Sprinkle IR MUPS Formulation of Rosuvastatin Calcium.

Sprinkle formulations represent an interesting concept of medicinal products aimed at the steadily growing population of patients suffering from swallowing difficulties (dysphagia). In the present work, immediate-release sprinkle MUPS (multiple-unit pellet system) containing rosuvastatin calcium as a model drug substance was successfully developed. The formulation was prepared by drug layering technique using novel calcium phosphate-based starting pellets (PharSQ® Spheres CM) of three different particle sizes. The study showed that the developed multiparticulates were characterized by uniform distribution of coating layers thickness, as well as fast dissolution rate (more than 85% of rosuvastatin calcium dissolved within 30 min, as required by the relevant USP/NF monograph). Rosuvastatin calcium, like other statins, has a bitter, unpleasant taste. Investigations conducted with an electronic tongue suggested that the developed formulation achieved the desired taste-masking efficiency. The effect was found to be particle size-dependent, improving as the size of the multiparticulates increased.

Orodispersible Films with Rupatadine Fumarate Enclosed in Ethylcellulose Microparticles as Drug Delivery Platform with Taste-Masking Effect.

Orally disintegrating (orodispersible) films provide a versatile tool for drug administration, especially in the pediatric and geriatric population, since they reduce the risk of choking and do not necessitate drinking water during application. By considering their direct contact with the taste buds, palatability is an influential aspect related to patient compliance. The microparticles based on taste-masking polymers containing drugs enclosed inside effectively mask the unpleasant taste of medicines. Ethylcellulose is a hydrophobic polymer widely used as a taste-masking material. Rupatadine fumarate, a second-generation antihistamine drug, is characterised by an intense bitter taste; therefore, it is crucial to achieve a tolerable taste whilst developing orodispersible formulations with its content. The objective of this study was to develop orally disintegrating films with rupatadine fumarate in the form of ethylcellulose-based microparticles obtained from aqueous dispersions of ethylcellulose-Surelease® or Aquacoat® ECD. It was a technological challenge to achieve homogenous drug content per dosage unit and sufficient mechanical properties for film operating due to the necessity to suspend the microparticles in the casting solution. Although the process of obtaining films consisted of several steps (mixing, pouring, drying), the particles were homogeneously dispersed, and each film of the desired size contained the proper dose of the drug. The taste-masking effect was also maintained. This parameter was confirmed by three independent methods: in vivo by healthy volunteers, an electronic tongue and a dissolution test. The applied taste-evaluation techniques showed that the films containing Aquacoat® ECD microparticles have the highest degree of bitter taste reduction, which confirms the results obtained in our previous studies.

Absolute lymphocyte count as a predictor of mortality and readmission in heart failure hospitalization.

Background: There is renewed interest in pursuing frugal and readily available laboratory markers to predict mortality and readmission in heart failure. We aim to determine the relationship between absolute lymphocyte count (ALC) and clinical outcomes in patients with heart failure hospitalization. Methods: This was a retrospective cohort study of patients with heart failure. Patients were divided into two groups based on ALC, less than or equal to 1500 cells/mm3 and > 1500 cells/ mm3. The primary outcome was all-cause mortality. We did subgroup analysis based on ejection fraction and studied the association between ALC categories and clinical outcomes. Both ALC groups are matched by propensity score, outcomes were analyzed by Cox regression, and estimates are presented in hazard ratios (HR) and 95% confidence intervals (CI). Results: We included 1029 patients in the pre-matched cohort and 766 patients in the propensity-score matched cohort. The median age was 64 years (IQR, 54-75), and 60.78% were male. In the matched cohort, ALC less than or equal to 1500 cells/mm3 had a higher risk of mortality compared with ALC > 1500 cells/mm3 (HR 1.51, 95% CI: 1.17-1.95; P = 0.002). These results were reproducible in subgroups of heart failure. When ALC was divided into four groups based on their levels, the lowest group of ALC had the highest risk of mortality. Conclusions: In patients with heart failure and both subgroups, ALC less than or equal to 1500 cells/mm3 had a higher risk of mortality. Patients in lower groups of the ALC categories had a higher risk of mortality.

Infective Endocarditis and Intravenous Drug Users: Never Was and Never Will Be Taken Lightly.

Infective endocarditis (IE) is the infection of the endocardial surface (innermost layer - valves, chordae tendineae, and papillary muscles) of the heart. It usually refers to infection of one or more of the heart valves which may be native or prosthetic. The definition also includes infection on indwelling cardiac devices. Over time, the etiology, as well as causes of IE, have evolved and doubled in numbers because of a greater number of patients with indwelling cardiac devices and central lines. Some characteristic features have remained the same, including intravenous drug users (IVDU) and right-sided IE, fever, or peripheral signs of IE. However, there are instances where the clinical presentation is unique. Here we describe an unusual case of an IVDU patient developing acute decompensated heart failure following acute aortic regurgitation (AR) from IE without fever and right-sided heart or tricuspid valve involvement.

Helicobacter pylori Resistance to Triple Therapy in a Multicultural Population in New York City.

INTRODUCTION: Helicobacter pylori infection (HPI) has become a worldwide concern due to its associations with intestinal and extraintestinal disease including cancer, autoimmune phenomena, and vitamin deficiencies. HPI has been found to affect Hispanics at higher rates compared with non-Hispanics in the USA. Hispanics comprise most of the patient population at Metropolitan Hospital in New York City. Growing concerns about antibiotic resistance led to the reconciliation of treatment guidelines with the consensus of bismuth quadruple therapy as the first-line treatment, replacing clarithromycin-based triple therapy. We conducted a retrospective study to explore the resistance rate of Helicobacter pylori to triple therapy in patients at Metropolitan Hospital. OBJECTIVE: To explore the resistance rates of Helicobacter pylori in infected patients treated with clarithromycin-based triple therapy in Metropolitan Hospital over a five-year period. MATERIALS AND METHODS: Charts of all patients who underwent upper endoscopy during a five-year period were retrospectively reviewed. Overall, 2000 patients were screened for presence of HPI. We included 322 patients with a demonstrated HPI obtained from biopsies taken during upper endoscopy within the study period. Inclusion criteria were patients older than 18 years old with positive HPI who were prescribed therapy. Exclusion criteria were patients with positive HPI who did not receive treatment for the infection and patients without a confirmatory diagnosis of infection. We further reported on three groups based on the implemented therapy. Each treated group was divided into three subgroups based on eradication testing. Treatment compliance was documented. The patient population was demographically characterized by ethnicity, age at diagnosis, body mass index (BMI), and sex. RESULTS: Of the 322 patients included in the study, 258 were Hispanics (80%). The eradication rate among patients treated with selected clarithromycin-based therapies was found to be statistically significant when compared with other HPI therapies. There was no statistically significant difference between the studied group with respect to age, sex, ethnicity, and BMI. In the group of patients with suspected clarithromycin resistance, antimicrobial sensitivity testing was ordered in one case. DISCUSSION: HPI varies with race and ethnicity. Within the USA, the prevalence is lowest among non-Hispanics. Ethnicity and age, sex, and BMI were not factors that impacted treatment outcomes. We found that triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin (PAC) was used as a first-line treatment, consistently showing a low rate of resistance. The eradication rate among patients treated with PAC was found to be statistically significant when compared with all other therapies. It is significant for the hospitals with limited resources, where initial treatment follows the "test-and-treat" strategy. Quadruple therapy as the first-line treatment raises concerns about medication costs, insurance coverage, side effects, and dosing, which may have a significant impact on patient compliance. CONCLUSION: Our study showed that selected clarithromycin-based therapies were superior for HPI eradication when compared with non-clarithromycin-based triple therapy in low-resistance communities. Culture with antimicrobial susceptibility testing was used in a de minimis number of cases, which raises awareness for future study.

Efficacy of corticosteroids in non-intensive care unit patients with COVID-19 pneumonia from the New York Metropolitan region.

INTRODUCTION: The role of systemic corticosteroid as a therapeutic agent for patients with COVID-19 pneumonia is controversial. OBJECTIVE: The purpose of this study was to evaluate the effect of corticosteroids in non-intensive care unit (ICU) patients with COVID-19 pneumonia complicated by acute hypoxemic respiratory failure (AHRF). METHODS: This was a single-center retrospective cohort study, from 16th March, 2020 to 30th April, 2020; final follow-up on 10th May, 2020. 265 patients consecutively admitted to the non-ICU wards with laboratory-confirmed COVID-19 pneumonia were screened for inclusion. 205 patients who developed AHRF (SpO2/FiO2 ≤ 440 or PaO2/FiO2 ≤ 300) were only included in the final study. Direct admission to the Intensive care unit (ICU), patients developing composite primary outcome within 24 hours of admission, and patients who never became hypoxic during their stay in the hospital were excluded. Patients were divided into two cohorts based on corticosteroid. The primary outcome was a composite of ICU transfer, intubation, or in-hospital mortality. Secondary outcomes were ICU transfer, intubation, in-hospital mortality, discharge, length of stay, and daily trend of SpO2/FiO2 (SF) ratio from the index date. Cox-proportional hazard regression was implemented to analyze the time to event outcomes. RESULT: Among 205 patients, 60 (29.27%) were treated with corticosteroid. The mean age was ~57 years, and ~75% were men. Thirteen patients (22.41%) developed a primary composite outcome in the corticosteroid cohort vs. 54 (37.5%) patients in the non-corticosteroid cohort (P = 0.039). The adjusted hazard ratio (HR) for the development of the composite primary outcome was 0.15 (95% CI, 0.07-0.33; P <0.001). The adjusted hazard ratio for ICU transfer was 0.16 (95% CI, 0.07 to 0.34; P < 0.001), intubation was 0.31 (95% CI, 0.14 to 0.70; P- 0.005), death was 0.53 (95% CI, 0.22 to 1.31; P- 0.172), composite of death or intubation was 0.31 (95% CI, 0.15 to 0.66; P- 0.002) and discharge was 3.65 (95% CI, 2.20 to 6.06; P<0.001). The corticosteroid cohort had increasing SpO2/FiO2 over time compared to the non-corticosteroid cohort who experience decreasing SpO2/FiO2 over time. CONCLUSION: Among non-ICU patients hospitalized with COVID-19 pneumonia complicated by AHRF, treatment with corticosteroid was associated with a significantly lower risk of the primary composite outcome of ICU transfer, intubation, or in-hospital death, composite of intubation or death and individual components of the primary outcome.

Utilization of Ethylcellulose Microparticles with Rupatadine Fumarate in Designing Orodispersible Minitablets with Taste Masking Effect.

Minitablets in orodispersible form constitute a flexible drug delivery tool for paediatric and geriatric population as they eliminate the risk of chocking and do not require drinking water in the application. Due to their direct contact with taste buds, taste sensation is an important factor. Preparing microparticles with taste masking polymers utilizing spray drying is an efficient technique for reducing the bitterness of drugs. Ethylcellulose is a hydrophobic polymer widely used as a taste masking material. Rupatadine fumarate, one of the newest antihistamines, features an intensive bitter taste, hence in designing orodispersible formulations, achieving an acceptable taste is a crucial issue. The main objective of this work was to formulate orodispersible minitablets containing taste masked ethylcellulose-based microparticles with rupatadine fumarate and evaluation of their quality, especially in terms of taste masking efficacy. The accessed data indicated that all obtained minitablets were characterized by beneficial pharmaceutical properties. Three independent methods: in vivo with healthy volunteers, in vitro drug dissolution, and "electronic tongue" confirmed that all designed formulations provided satisfactory taste masking rate and that formulation F15 (prepared with Pearlitol® Flash and Surelease® microparticles with rupatadine fumarate) was characterized by the lowest bitterness score.

Ethylcellulose in Organic Solution or Aqueous Dispersion Form in Designing Taste-Masked Microparticles by the Spray Drying Technique with a Model Bitter Drug: Rupatadine Fumarate.

The taste of drugs is an important factor affecting pharmacotherapy effectiveness, and obtaining formulations with acceptable organoleptic properties is still an ongoing issue in pharmaceutical technology. One of the innovative methods of taste masking is preparation of microparticles by the spray drying technique, utilizing polymers with different physicochemical properties. Rupatadine fumarate (RUP) is one of the newest antihistamines, with an innovative and multidirectional mechanism of action, and an extremely bitter taste. The aim of this work was to investigate the feasibility of utilizing organic or aqueous forms of ethylcellulose (EC) for the preparation of microparticles with RUP by the spray drying technique. Spray dried samples at different drug:polymer ratios were prepared using organic solution (Ethocel®) or aqueous dispersions of EC (Surelease®, Aquacoat® ECD). Evaluation of the taste masking efficacy was performed in vivo in human taste panel, in vitro based on dissolution test, and by self-constructed electronic tongue. It was shown that microparticles obtained from aqueous dispersions of EC have superior pharmaceutical properties in terms of both morphology and taste masking efficacy in comparison to those obtained from organic solution.

Cyclodextrins Based Electrochemical Sensors for Biomedical and Pharmaceutical Analysis.

Electrochemical sensors are very convenient devices, as they may be used in a lot of fields starting from the food industry to environmental monitoring and medical diagnostics. They offer the values of simple design, reversible and reproducible measurements, as well as ensuring precise and accurate analytical information. Compared with other methods, electrochemical sensors are relatively simple as well as having low costs, which has led to intensive development, especially in the field of medicine and pharmaceuticals within the last decade. Recently, the number of publications covering the determination of aminoacids, dopamine, cholesterol, uric acid, biomarkers, vitamins and other pharmaceutical and biological compounds has significantly increased. Many possible types of such sensors and biosensors have been proposed: owing to the kind of the detection-potentiometric voltametric, amperometry, and the materials that can be used for, e.g. designing molecular architecture of the electrode/solution interface, carbon paste, carbon nanotubes, glass carbon, graphite, graphene, PVC, conductive polymers and/or nanoparticles. The active compounds which provide the complex formation with analyte (in the case of non-current techniques) or activate biomolecules electrochemically by particle recognition and selective preconcentration of analyte on the electrode surface (in the case of current techniques) are the most recently used cyclodextrins. These macrocyclic compounds have the ability to interact with a large diversity of guest particles to form complexes of the type of guest host, for example, with particles from drugs, biomolecules, through their hydrophilic outer surface and lipophilic inner cavities. Cyclodextrins have been the subject of frequent electrochemical studies that focused mostly on both their interactions in a solid state and in solution. The process of preparing of CDs modified electrodes would, consequently, open new avenues for new electrochemical sensors and, therefore, widen their use in biomedical and drug analysis. This review presents information on manufacturing techniques and performances of these sensors and biosensors. The opportunities for these sensors to carry out biomedical and pharmaceutical researches are demonstrated.

Functionalized ß-cyclodextrin based potentiometric sensor for naproxen determination.

Potentiometric sensors based on neutral ß-cyclodextrins: (2-hydroxypropyl)-ß-cyclodextrin, heptakis(2,3,6-tri-O-methyl)-ß-cyclodextrin, heptakis(2,3,6-tri-O-benzoyl)-ß-cyclodextrin and anionic ß-cyclodextrin: (2-hydroxy-3-N,N,N-trimethylamino)propyl-ß-cyclodextrin chloride for naproxen are described. Inclusion complexes of naproxen with the above-mentioned cyclodextrins were studied using IR spectroscopy. The electrode surface was made from PVC membranes doped with the appropriate ß-cyclodextrin as ionophores and quaternary ammonium chlorides as positive charge additives that were dispersed in plasticizers. The optimum membrane contains heptakis(2,3,6-tri-O-benzoyl)-ß-cyclodextrin, o-nitrophenyloctyl ether and tetraoctyl ammonium chloride as a lipophilic salt. The electrode is characterized by a Nernstian response slope of -59.0 ± 0.5 mV decade(-1) over the linear range of 5.0 × 10(-5)-1.0 × 10(-2) mol L(-1) and the detection limit 1.0 × 10(-5) mol L(-1), as well as the response time 10s. It can be used in the pH range 6.2-8.5 for 10 months without any considerable deterioration. Incorporation of ß-cyclodextrins improved the electrode selectivity towards naproxen ions from several inorganic and organic interferents and some common drug excipients due to concovalent interactions (host molecule-guest molecule). The notable advantages of the naproxen-selective electrode include its high sensitivity, high selectivity, cost-effectiveness as well as accurate and comfortable application in drug analysis and milk samples.

A new potentiometric electrode incorporating functionalized ß-cyclodextrins for diclofenac determination.

This paper reports the preparation of diclofenac-selective membrane electrodes incorporating ß-cyclodextrins: (2-hydroxypropyl)-ß-cyclodextrin, heptakis(2,3,6-tri-O-methyl)-ß-cyclodextrin, and heptakis(2,3,6-tri-O-benzoyl)-ß-cyclodextrin. Several plasticized poly(vinyl chloride) membranes of different compositions were tested with the best electrode being the one incorporating heptakis(2,3,6-tri-O-benzoyl)-ß-cyclodextrin with the membrane plasticized with 2-nitrophenyloctyl ether. The electrode is characterized by a near-Nernstian response slope of -60.0 mV decade(-1) over the linear range of 5.0×10(-5)-1.0×10(-2) mol L(-1) and a limit of detection of 1.4×10(-5) mol L(-1). The proposed electrode can easily discriminate diclofenac ions from several inorganic and organic interferents and some common drug excipients. The electrode has a response time of 10s and can be used within a pH range of 6.2-8.5 over 10 months without any considerable deterioration. The electrical properties of the membrane electrode were studied by impedance spectroscopy. The notable advantages of the diclofenac-selective electrode include its high sensitivity, selectivity, cost-effectiveness, and comfortable application in drug and urine analysis.

Preparation and characterization of a sulindac sensor based on PVC/TOA-SUL membrane.

A potentiometric sulindac sensitive sensor based on tetraoctylammonium (Z)-5-fluoro-2-methyl-1-[[p-(methylsulfinyl)phenyl]methylene]-1H-indene-3-acetate (TOA-SUL) was described. The electrode responded with sensitivity of 57.5±1.6mV decade(-1) over the linear range 5×10(-5)-1×10(-2)mol L(-1) at pH6.0-9.0. It had the limit of detection 1.4×10(-5)mol L(-1), a fast response time of 13s and showed clear discrimination of sulindac ions from several inorganic and organic compounds and also amino acids. This electrode did not contain any inner solutions, so it was easy and comfortable to use. The proposed sensor was used to determine sulindac in clear solution and in urine sample solution.

Preparation and study of a naproxen ion-selective electrode.

Naproxen membrane electrodes based on different plasticizers and quaternary ammonium salt tetraoctylammonium (S)-6-methoxy-α-methyl-2-naphthaleneacetate (NAP-TOA) were prepared. The electrode response to naproxen has the sensitivity of -59.2 mV decade(-1) over the linear range of 10(-4)-10(-1) mol L(-1) and limit of detection 1.80×10(-5) mol L(-1). This electrode has a response time 15-20s and can be used in the pH range 5.5-9.5. The selective coefficients were determined in relation to some organic and inorganic anions and excipients of pharmaceuticals. The notable property and attractive quality of the naproxen electrode are low cost, comfortable application and very long lifetime-about 20 months. The electrode was successfully applied for determination of naproxen in urine samples and pharmaceuticals by the calibration curve method and standard addition method. The obtained results are comparable and sometimes better than those obtained by pharmacopoeial method.

Ketoprofen ion-selective electrode and its application to pharmaceutical analysis.

The composition of a polymeric potential-determining phase for ketoprofen selective electrode has been determined and the following basic electrode parameters were examined: measurement range, slope characteristic, limit of detection, response time, lifetime and selectivity coefficients in relation to some organic and inorganic anions. The electrode have been used for ketoprofen determination in the range 25.43-25430 microg/mL.

Naproxen ion-selective electrode and its application to pharmaceutical analysis.

An ion-selective membrane electrode was prepared based on ion-pair complex of naproxen with methyltrioctylammonium. Its basic analytical parameters such as: slope characteristics, measuring range, detection limit, response time, life time were determined. The electrode showed Nernstian response from the 10(-1) to 10(-4) mol l(-1) concentration range and 5.5-8.5 pH range, low limit of detection 5 x 10(-5) mol l(-1) and short response time--20s. Selectivity was good over a number of organic and inorganic anions. The electrode was applied for the determination of naproxen tablets in aqueous solutions by the calibration curve method and standard addition method.