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1.
Georgian Med News ; (306): 184-188, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33130670

RESUMO

Currently, central nervous and cardiovascular system disorders of hypoxia genesis are widely treated with drugs that restore blood flow, as well as drugs that affect cell metabolism, namely, individual units of adaptive molecular-biochemical reactions. Of particular interest are pharma-correction methods of affecting synthesis and expression of Klotho proteins, such as vitamin D and Necrostatin-1, estrogens. The purpose of the study was to identify the ability of vitamin D and tamoxifen estrogen receptor modulator to affect Klotho protein synthesis (under hypoxia in vitro modeling in brain and heart cells). The study was performed on sexually mature white non-linear rats - males weighing 190-230 g. Hypoxia in vitro was modeled by insertion of 0.6 µM concentration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridil (MPTP) into the suspension of respiratory tract tissue differentiator cardiomyocytes. By means of immunoenzyme analysis, concentration of Nitrotyrosin (Ntz) (ELISA Kit "Hycult biotechnology b.v.") and Klotho protein (Elabscience, USA) in cell suspensions was evaluated. Statistical processing of the results was carried out using the STATISTICA® for Windows 6.0 program (StatSoft Inc., No. AXXR712D833214FAN5). The reliability of the differences was carried out using the Student's t-criterion. The data analysis demonstrated that a 120-minute MPTP incubation of cardiomyocytes and neurocytes resulted in a significant deficiency of Klotho protein concentration compared to intact suspensions. Such a decrease, in our opinion, is related to the development of oxidative stress in cell suspension (increase of Ntz by 65% ​​and 69% in the cardiomyocyte and neurocyte suspensions, respectively), as well as hyperproduction of proinflammatory cytokines such as tumor necrosis factor (TNF) and interferon (INF). Vitamin D (10-7) addition to the incubation medium of cardiomyocytes and neurocytes resulted in the increase of Klotho protein content by 56% on average, with 36% and 42% reduction of Ntz concentration, respectively. The registered effects of vitamin D are explained with its direct stimulating of the expression and synthesis of Klotho protein and limiting FGF23 hyperproduction. The introduction of tamoxifen estrogen receptor modulator (10-7) into the cardio- and neurocyte incubation medium did not affect Klotho protein concentration (an increase in concentration of 34% and 28% respectively) in advanced cell suspensions as much as vitamin D, however, nitrotyrosine concentration decrease made a more expressed impact, on average by 52% and 60%. The effects of tamoxifen are implemented due to its impact on the HSP proteins system, which provides the structural and functional integrity of the Klotho protein.


Assuntos
Hipóxia , Miócitos Cardíacos , Animais , Glucuronidase , Humanos , Masculino , Ratos , Reprodutibilidade dos Testes , Suspensões
2.
Water Sci Technol ; 82(9): 1868-1876, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33201850

RESUMO

The effect of ethylated soy protein-based bioflocculant (EtSP) as a filter aid reagent was investigated. The efficiency of EtSP as a filter aid was evaluated in terms of the specific cake resistance, α, and was compared with chitosan and polyaluminum chloride (PAC). Diatomite and kaolin were used as model particles. Total filtration resistance, R, decreased with increasing flocculant dosage (wt.%, flocculant/particle) and was almost constant in the range of 1 wt.% or more for both particles. The α value was significantly decreased from 1.01 × 1011 to 9.01 × 1010 m/kg for diatomite and from 5.11 × 1010 to 5.20 × 109 m/kg for kaolin by the addition of EtSP in the case of 1.0 wt.%. The α value for cakes formed by EtSP was much smaller than that formed by chitosan and PAC. In the case of diatomite, in the dose range of 0.5-1.0 wt.%, the α value for cakes formed by EtSP and chitosan was almost the same. However, at the excess dose of 2.0 wt.% over, the α value formed by chitosan abruptly increased. In the case of kaolin, in the dose range of 1.0-2.0 wt.%, the α values of chitosan and PAC were mostly the same, however, these values were larger by ca. nine times than that of EtSP.


Assuntos
Caulim , Proteínas de Soja , Terra de Diatomáceas , Floculação , Suspensões
3.
Int J Nanomedicine ; 15: 7601-7613, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116490

RESUMO

Introduction: Etoposide refers to a derivative of podophyllotoxin, which plays an important role in the treatment of cancer due to its prominent anti-tumor effect. As a BCS IV drug, etoposide exhibits insufficient aqueous solubility and permeability, thereby limiting its oral absorption. To enhance the oral bioavailability of etoposide, this study developed an amorphous nanopowder. Methods: Based on preliminary screening and experimental design, the stabilizer and preparation process of etoposide nanosuspension were explored. Subsequently, using a Box-Behnken design, the effects of independent factors (ultrasonication time, ratio of two phases and stabilizer concentration) on response variables (particle size and polydispersity index) were studied, and then the formulation was optimized. Finally, nanosuspension was further freeze dried with 1% of mannitol resulting in the formation of etoposide amorphous nanopowder. Results: The optimized etoposide nanopowder showed as spherical particles with an average particle size and polydispersity index of 211.7 ± 10.4 nm and 0.125 ± 0.028. X-ray powder diffraction and differential scanning calorimetry confirmed the ETO in the nanopowder was amorphous. Compared with coarse powder and physical mixture, etoposide nanopowder achieved significantly enhanced saturated solubility and dissolution in various pH environments. The Cmax and AUC0-t of etoposide nanopowder after oral administration in rats were respectively 2.21 and 2.13 times higher than the crude etoposide suspension. Additionally, the Tmax value of nanopowder was 0.25 h, compared with 0.5 h of reference group. Discussion: In the present study, the optimized amorphous nanopowder could significantly facilitate the dissolution and oral absorption of etoposide and might act as an effective delivery method to enhance its oral bioavailability.


Assuntos
Composição de Medicamentos , Etoposídeo/administração & dosagem , Etoposídeo/farmacologia , Nanopartículas/química , Administração Oral , Análise de Variância , Animais , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Cristalização , Etoposídeo/química , Etoposídeo/farmacocinética , Liofilização , Masculino , Modelos Estatísticos , Tamanho da Partícula , Permeabilidade , Pós , Ratos Sprague-Dawley , Solubilidade , Solventes , Suspensões , Difração de Raios X
4.
Int J Pharm Compd ; 24(5): 413-419, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32886640

RESUMO

Allopurinol is an orally administered inhibitor of xanthine oxidase used primarily in the treatment of hyperuricemia associated with gout. Allopurinol reduces serum and urinary uric acid concentrations. Its use should be individualized for each patient. The dosage of allopurinol to accomplish full control of gout and to lower serum uric acid to normal or near-normal levels varies with the severity of the disease, and needs to be flexible to permit precise, customized dose titration for individual patients. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of allopurinol currently exists. Allopurinol is commercially available as 100-mg and 300-mg scored tablets. An extemporaneously compounded suspension from pure drug powder or commercial tablets would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical stability of extemporaneously compounded allopurinol suspensions in the PCCA Base SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two allopurinol concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating ultra-performance liquid chromatography assay for the determination of the chemical stability of allopurinol in SuspendIt was developed and validated. Suspensions of allopurinol were prepared in SuspendIt at 10.0-mg/mL and 20.0-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic amber prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially and at the following time points: 7 days, 14 days, 30 days, 45 days, 60 days, 88 days, 120 days, and 182 days. Physical data such as pH, viscosity, and appearance were also noted. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period. The study showed that allopurinol concentrations did not go below 93% of the label claim (initial drug concentration) at both temperatures studied. Viscosity and pH values also did not change significantly. This study demonstrates that allopurinol is physically and chemically stable in SuspendIt for 180 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for allopurinol in a liquid dosage form, with an extended beyond-use-date to meet patient needs.


Assuntos
Alopurinol , Ácido Úrico , Administração Oral , Alopurinol/química , Alopurinol/farmacologia , Cromatografia Líquida de Alta Pressão , Composição de Medicamentos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Humanos , Suspensões , Ácido Úrico/química
5.
J Environ Manage ; 271: 110970, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32778274

RESUMO

The concentrative isolation of metal traces from aqueous solutions is of vital importance for environmental and industrial processes. Developing reliable systems of nanoscale that can be fine-tuned to effectively isolate these metals remains an intriguing aim which can potentially beget economic benefits and mitigate major environmental concerns. Here we demonstrate a conceptual metal extraction system where magnetic multi-wall carbon nanotubes (M-MWCNTs) are surface-equipped with a molecular network of polyethylenimine (PEI) to serve as a reusable nano-ionic exchanger, referred to as "M-MWCNTs-PEI". The designed nano-ionic exchanger forms readily stable suspensions with the metal-bearing aqueous solutions eliminating the need for vigorous agitation. Besides, it can be magnetically manipulated and separated in/from the solution. To exemplify its potential for the isolation of metal traces, the M-MWCNTs-PEI was tested with the uranium trace ions in aqueous media. The M-MWCNTs-PEI featured distinct sorption capacity of ~488 mg/g at pH 6, with moderate, but stable, binding affinity toward uranium ions. As such, excellent isolation performance is demonstrated while bound uranium ions are effectively concentrated and recovered from the interfacial PEI molecular network. This was efficiently achieved by exposing the loaded M-MWCNTs-PEI to solutions of small volumes and specific chemistry. Such combined qualities of large capacity and reusability have not been observed with the previously reported ion exchange systems. Altogether, our observations here demonstrate how functional systems of nanoscale can be adapted for industrial applications while this concept can be extended to address other important resources such as rare-earth and lanthanide elements.


Assuntos
Nanotubos de Carbono , Urânio , Adsorção , Concentração de Íons de Hidrogênio , Cinética , Fenômenos Magnéticos , Soluções , Suspensões
7.
Int J Nanomedicine ; 15: 4225-4236, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606674

RESUMO

Introduction: The aim of the study was to optimize the processing factors of precipitation-ultrasonication technique to prepare nano-sized particles of Lovastatin (LA) for enhancing its solubility, dissolution rate and in vivo bioavailability. Methods: LA nanoparticles (LANs) were prepared using precipitation-ultrasonication technique under different processing factors. LANs were characterized in terms of particle size, zeta potential and in vitro release. Stability studies at 4°C, 25°C and 40°C were conducted for optimum formulation. In addition, the in vivo bioavailability of the optimum formula was studied in comparison to a marketed product in white master rats. Results: The optimized LAN formula (LAN15) had particle size (190±15), polydispersity index (0.626±0.11) and a zeta potential (-25±1.9 mV). The dissolution study of the nanosuspensions showed significant enhancement compared with pure drug. After 50 min, only 20.12±1.85% of LA was dissolved while 99.1±1.09% of LA was released from LAN15. Stability studies verified that nanosuspensions at 4°C and 25°C showed higher stability with no particle growth compared to the samples studied at 40°C. In vivo studies conducted in rats verified that there was 1.45-fold enhancement of Cmax of LAN15 as compared to marketed tablets. Conclusion: Nanoparticle prepared by ultrasonication-assisted precipitation method is a promising formula for enhancing the solubility and hence the bioavailability of Lovastatin.


Assuntos
Lovastatina/farmacologia , Nanopartículas/química , Administração Oral , Animais , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Lovastatina/sangue , Lovastatina/química , Lovastatina/farmacocinética , Masculino , Tamanho da Partícula , Ratos Wistar , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Suspensões
8.
PLoS One ; 15(7): e0236599, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32722685

RESUMO

The increasing prevalence of carbon nanotubes (CNTs) as components of new functional materials has the unintended consequence of causing increases in CNT concentrations in aqueous environments. Aqueous systems are reservoirs for bacteria, including human and animal pathogens, that can form biofilms. At high concentrations, CNTs have been shown to display biocidal effects; however, at low concentrations, the interaction between CNTs and bacteria is more complicated, and antimicrobial action is highly dependent upon the properties of the CNTs in suspension. Here, impact of low concentrations of multiwalled CNTs (MWCNTs) on the biofilm-forming opportunistic human pathogen Pseudomonas aeruginosa is studied. Using phase contrast and confocal microscopy, flow cytometry, and antibiotic tolerance assays, it is found that sub-lethal concentrations (2 mg/L) of MWCNTs promote aggregation of P. aeruginosa into multicellular clusters. However, the antibiotic tolerance of these "young" bacterial-CNT aggregates is similar to that of CNT-free cultures. Overall, our results indicate that the co-occurrence of MWCNTs and P. aeruginosa in aqueous systems, which promotes the increased number and size of bacterial aggregates, could increase the dose to which humans or animals are exposed.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Nanotubos de Carbono/química , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Suspensões
9.
Water Res ; 183: 116070, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32622236

RESUMO

The influence of the pre-ozonization on the formation of disinfection by-products (DBPs) upon chlorination for fresh waters containing three common cyanobacteria, namely Microcystis aeruginosa, Anabaena aequalis and Oscillatoria tenuis at 10,000 cells/mL is reported. Specifically, the formation carbonaceous-DBPs (C-DBPs) (trihalomethanes (THMs), haloacetic acids (HAAs) and haloketones (HKs)) and nitrogenous-DBPs (N-DBP) (haloacetonitriles (HAN) and trichloronitromethane (TCNM)) has been determined as a function of the pH (6.5 or 8.0 and bromide ion concentration (300 µg/L). The main C-DBPs were THMs and HAAs with negligible formation of HKs accompanied by minor amounts of HANs in the absence of TCNM. Pre-ozonation of the aqueous cyanobacteria suspensions does not allow a control over all the DBPs. In fact, pre-ozonation increases THM formation and generates TCNM, has low influence on HAAs and only decreases the formation of HANs. The overall conclusion of this work is that pre-ozonation of waters containing a relatively low concentration of common fresh water cyanobacteria is not an appropriate process to decrease DBP formation from chlorine. Cyanobacteria removal from raw water before chlorination or ozonation should reduce DBP formation.


Assuntos
Cianobactérias , Desinfetantes , Microcystis , Oscillatoria , Ozônio , Poluentes Químicos da Água/análise , Purificação da Água , Anabaena , Cloro , Desinfecção , Halogenação , Suspensões , Trialometanos/análise
10.
Appl Environ Microbiol ; 86(18)2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32680860

RESUMO

Temperature and relative humidity are major factors determining virus inactivation in the environment. This article reviews inactivation data regarding coronaviruses on surfaces and in liquids from published studies and develops secondary models to predict coronaviruses inactivation as a function of temperature and relative humidity. A total of 102 D values (i.e., the time to obtain a log10 reduction of virus infectivity), including values for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were collected from 26 published studies. The values obtained from the different coronaviruses and studies were found to be generally consistent. Five different models were fitted to the global data set of D values. The most appropriate model considered temperature and relative humidity. A spreadsheet predicting the inactivation of coronaviruses and the associated uncertainty is presented and can be used to predict virus inactivation for untested temperatures, time points, or any coronavirus strains belonging to Alphacoronavirus and Betacoronavirus genera.IMPORTANCE The prediction of the persistence of SARS-CoV-2 on fomites is essential in investigating the importance of contact transmission. This study collects available information on inactivation kinetics of coronaviruses in both solid and liquid fomites and creates a mathematical model for the impact of temperature and relative humidity on virus persistence. The predictions of the model can support more robust decision-making and could be useful in various public health contexts. A calculator for the natural clearance of SARS-CoV-2 depending on temperature and relative humidity could be a valuable operational tool for public authorities.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/virologia , Modelos Biológicos , Pneumonia Viral/virologia , Inativação de Vírus , Fômites/virologia , Humanos , Umidade , Pandemias , Saúde Pública , Suspensões , Temperatura
11.
Chemosphere ; 259: 127510, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32650172

RESUMO

Intensive application of biochar requires better understanding of their environmental behaviors such as stability, fate, and mobility. The release of bulk biochar into biochar nanoparticles (NPs) may bring risks because of their potential flowing into downstream water bodies with nutrients/containments attached. Low-temperature pyrolyzed biochars, namely fruit tree branch biochar of 350/450/550 °C (FB350, FB450 and FB550), corn straw biochar of 350 °C (CB350) and peanut straw biochar of 350 °C (PB350), were produced, and their NPs were extracted. The yield, elemental composition, mineral composition, surface functional groups and zeta potential of biochar NPs were characterized. Subsequently their suspension stability was evaluated in NaCl and CaCl2 solutions by dynamic light scattering technique. The Hamaker constants and particle interaction energy of the biochar NPs were calculated by adopting Derjaguin-Landau-Verwey-Overbeek theory. For biochar NPs of same feedstock, the stability of FB350/450/550-NPs could be predicted well by their zeta potential values. The types of their surface functional groups were the same while their adsorption intensity differed. The scenarios for biochar NPs of different feedstock sources were different, that is, inconsistent variation was observed between their zeta potential and suspension stability, which were rooted in the variable type and quantity of surface functional groups. In conclusion, feedstock was the most significant factor that influenced the suspension stability of biochar NPs, followed by the pyrolysis temperature and solution chemistry, which were highly dependent on surface potential. The findings provide references for the environmental risk evaluation of biochar NPs and reasonable application of biochar in field.


Assuntos
Carvão Vegetal/química , Nanopartículas/química , Temperatura , Adsorção , Difusão Dinâmica da Luz , Pirólise , Soluções/química , Propriedades de Superfície , Suspensões/química
12.
Int J Pharm Compd ; 24(4): 327-336, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649306

RESUMO

Extemporaneous compounding in veterinary practice sometimes represents the only possibility for treating animals in the absence of appropriate commercial formulations, especially for particular species. This method involves manipulating pharmaceutical active ingredients to a suitable dosage and formulation for administration to humans or animals. However, veterinarians and pharmacists should focus on the risk of potential incompatibilities and instability of their preparations. To help practitioners in drug compounding, we investigated the stability of oral suspensions of tramadol, fluoxetine, and doxycycline in a commercial ready-to-use vehicle (SyrSpend). A validated high-performance liquid chromatography method was developed to assay these active pharmaceutical ingredients. The oral suspensions were prepared at two concentration ranges and were stored in amber glass bottles under refrigerated conditions and at room temperature. After 90 days, the average recovery rates were between 90% and 110% for tramadol (5 mg/mL to 30 mg/mL) and doxycycline  (2 mg/mL to 10 mg/mL) without organoleptic modification. For fluoxetine, only the formulation at 2 mg/mL was stable; at higher concentrations, the uniformity of the suspension was compromised.


Assuntos
Amido , Administração Oral , Cromatografia Líquida de Alta Pressão , Doxiciclina , Composição de Medicamentos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Fluoxetina , Humanos , Suspensões , Tramadol
13.
Zhongguo Zhong Yao Za Zhi ; 45(7): 1657-1663, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32489046

RESUMO

To prepare ginkgolide B nanosuspension(GB-NS), and investigate its dissolution behaviors in vitro. The miniaturized media milling method was used to prepare nanosuspensions, with average particle size and polydispersity index as the evaluation indexes. The formulation and process of GB-NS were optimized by single factor experiment and Box-Behnken design-response surface method. The morphology was observed by scanning electron microscope(SEM), and thecrystallinity of GB-NS was investigated by X-rays diffraction(XRD). The paddle method was used to study the dissolution of GB-NS in vitro. The mean particle size of optimized GB-NS was(180±7) nm, with a polydispersity index of 0.196±0.036. SEM showed that GB-NS was rod-like or irregular granular. XRD showed that the crystallinity of GB-NS was significantly reduced compared with GB raw material. The cumulative dissolution rate of GB-NS reached 90% in 30 min, which was higher than that of GB raw material. The findings suggested that the miniaturized media milling method was simple, efficient and feasible to prepare GB-NS. And the dissolution rate of GB was significantly improved by nanosuspension technology.


Assuntos
Nanotecnologia , Ginkgolídeos , Lactonas , Nanopartículas , Tamanho da Partícula , Solubilidade , Suspensões
14.
Clin Transl Sci ; 13(5): 880-885, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32475019

RESUMO

Since December 2019, a novel coronavirus (severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2)) infection has been rapidly spreading worldwide and causing the respiratory illness, coronavirus disease 2019 (COVID-19). The antiretroviral drug favipiravir (FPV) has been experimentally used for COVID-19 treatment since March 2020 in Japan. However, the pharmacokinetics of FPV in critically ill patients is unknown. We measured the serum concentration of FPV using high-performance liquid chromatography in patients with severe COVID-19 who were admitted to the intensive care unit and placed on mechanical ventilation. The patients were administered 1,600 mg of FPV twice daily on day 1, followed by 600 mg twice daily from day 2 to day 5 (or more if needed). Suspensions of FPV tablets were administered through a nasogastric tube. Seven patients were enrolled in this study. Forty-nine blood samples were obtained from the eligible patients to evaluate FPV concentration. The FPV trough (after 8-12 hours) concentrations of most samples were lower than the lower limit of quantification (1 µg/mL) and half-maximal effective concentration (9.7 µg/mL) against SARS-CoV-2 previously tested in vitro. FPV trough concentration in critically ill patients was much lower than that of healthy subjects in a previous clinical trial, which is a cause for great concern. Further study is required to determine the optimal strategy for treatment of patients with severe COVID-19.


Assuntos
Amidas/farmacocinética , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/tratamento farmacológico , Estado Terminal/terapia , Pneumonia Viral/tratamento farmacológico , Pirazinas/farmacocinética , Adulto , Idoso , Amidas/administração & dosagem , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Intubação Gastrointestinal , Masculino , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Pirazinas/administração & dosagem , Respiração Artificial , Índice de Gravidade de Doença , Suspensões , Comprimidos , Resultado do Tratamento
15.
Stud Health Technol Inform ; 270: 407-411, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32570416

RESUMO

The geographical imbalance of the healthcare workforce is a social problem in Japan. Except for big cities, hospitals have difficulties in securing a sufficient workforce to offer healthcare services stably. For local government, hospital service suspensions are potentially an essential indicator to figure out the capacity of the regional healthcare supply. This paper proposes an algorithm that automatically identifies and classifies hospital service suspensions from insurance claims data, based on periodicity and similarity. To verify the effectiveness, we have applied the algorithm to the insurance claim dataset, which has been provided 91 regional public insurers in Japan. The case studies have confirmed that the proposed algorithm has presented an evidential picture of hospital service suspensions, which is potentially useful to understand the actual capacity of healthcare service supply in regions.


Assuntos
Assistência à Saúde , Serviços de Saúde , Japão , Suspensões
16.
Emerg Infect Dis ; 26(9)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32568661

RESUMO

We aerosolized severe acute respiratory syndrome coronavirus 2 and determined that its dynamic aerosol efficiency surpassed those of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome. Although we performed experiment only once across several laboratories, our findings suggest retained infectivity and virion integrity for up to 16 hours in respirable-sized aerosols.


Assuntos
Aerossóis/isolamento & purificação , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/transmissão , Transmissão de Doença Infecciosa , Pneumonia Viral/transmissão , Suspensões/isolamento & purificação , Infecções por Coronavirus/virologia , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Pandemias , Pneumonia Viral/virologia
17.
Pharm Res ; 37(6): 92, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32394200

RESUMO

PURPOSE: The aim of the study was to evaluate organogel nanoparticles as a lipophilic vehicle to increase the oral bioavailability of poorly soluble compounds. Efavirenz (EFV), a Biopharmaceutical Classification System (BCS) Class II, was used as drug model. METHODS: Organogel nanoparticles loaded with EFV were formulated with sunflower oil, 12-hydroxystearic acid (HSA) and polyvinyl alcohol (PVA). Various parameters have been investigated in the current study such as (i) the release profile of organogel assessed by USP 4 cell flow dialysis, (ii) the impact of organogel on intestinal absorption, using Caco-2 cells as in vitro model and jejunum segments as ex vivo assay and (iii) the bioavailability of organogel following oral pharmacokinetic study. RESULTS: 250-300 nm spherical particles with a final concentration of 4.75 mg/mL drug loading were obtained, corresponding to a thousand fold increase in EFV solubility, combined to a very high encapsulation efficiency (>99.8%). Due to rapid diffusion, drug was immediately released from the nanoparticles. The biopharmaceutical evaluation on ex vivo jejunum segments demonstrated an increased absorption of EFV from organogel nanoparticles compare to a native EFV suspension. In vitro assays combining Caco-2 cell cultures with TEM and confocal microscopy demonstrated passive diffusion, while paracellular integrity and endocytosis activity remain expelled. Oral pharmacokinetics of EFV organogel nanoparticles improve oral bioavailability (Fr: 249%) and quick absorption compared to EFV suspension. CONCLUSION: Organogel nanoparticles increase the bioavailability of BCS Class II drugs. The main phenomena is simply oil transfer from the gelled particles through the cell membrane.


Assuntos
Benzoxazinas/química , Portadores de Fármacos/química , Géis/química , Nanocápsulas/química , Álcool de Polivinil/química , Ácidos Esteáricos/química , Óleo de Girassol/química , Animais , Benzoxazinas/administração & dosagem , Benzoxazinas/farmacocinética , Disponibilidade Biológica , Células CACO-2 , Permeabilidade da Membrana Celular , Sobrevivência Celular/efeitos dos fármacos , Difusão , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Excipientes/química , Humanos , Absorção Intestinal , Masculino , Solubilidade , Suspensões/química , Distribuição Tecidual
18.
Pharm Res ; 37(6): 97, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409985

RESUMO

PURPOSE: Subcutaneously or intramuscularly administered biodegradable microsphere formulations have been successfully exploited in the management of chronic conditions for over two decades, yet mechanistic understanding of the impact of formulation attributes on in vivo absorption rate from such systems is still in its infancy. METHODS: Suspension formulation physicochemical attributes may impact particulate deposition in subcutaneous (s.c.) tissue. Hence, the utility of synchrotron X-ray micro-computed tomography (µCT) for assessment of spatial distribution of suspension formulation components (PLG microspheres and vehicle) was evaluated in a porcine s.c. tissue model. Optical imaging of dyed vehicle and subsequent microscopic assessment of microsphere deposition was performed in parallel to compare the two approaches. RESULTS: Our findings demonstrate that synchrotron µCT can be applied to the assessment of microsphere and vehicle distribution in s.c. tissue, and that microspheres can also be visualised in the absence of contrast agent using this approach. The technique was deemed superior to optical imaging of macrotomy for the characterisation of microsphere deposition owing to its non-invasive nature and relatively rapid data acquisition time. CONCLUSIONS: The method outlined in this study provides a proof of concept feasibility for µCT application to determining the vehicle and suspended PLG microspheres fate following s.c. injection. A potential application for our findings is understanding the impact of injection, device and formulation variables on initial and temporal depot geometry in pre-clinical or ex-vivo models that can inform product design. Graphical abstract.


Assuntos
Materiais Biocompatíveis/química , Meios de Contraste/química , Microesferas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Suspensões/química , Tomografia Computadorizada por Raios X/métodos , Animais , Composição de Medicamentos , Imageamento Tridimensional , Injeções Subcutâneas , Intensificação de Imagem Radiográfica , Suínos , Síncrotrons , Tecidos Suporte/química
19.
AAPS PharmSciTech ; 21(5): 155, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32449139

RESUMO

One of the conventional methods of alleviating the problem of poor drug solubility is the particle size reduction. The efficiency of this approach depends on successful formulation suppressing the drug agglomeration. The aim of this study was to circumvent the dissolution problems of model hydrophobic meloxicam drug (MLX) by using liquid media of different wetting capacity to comminute and formulate a rapidly dissolving carrier system without the use of surfactants. Micro-suspensions of MLX were prepared by ball milling, using water or n-Heptane as a liquid medium. The suspensions were used as granulation liquids to formulate granulate from microcrystalline cellulose and lactose mixture. The release kinetics from prepared granulates were studied using the USP-4 dissolution apparatus. Micro-suspensions prepared via wet milling in non-water liquid media exhibited a massive improvement of release rate compared with source meloxicam and they outperformed their water-milled counterparts. The release rates from those formulations, despite not comprising any surfactant, were comparable to those obtained by different authors using surfactant stabilized nanosuspension formulations. Thus, they can present an interesting formulation alternative for hydrophobic drugs that are dissolution limited.


Assuntos
Portadores de Fármacos/química , Meloxicam/administração & dosagem , Celulose , Liberação Controlada de Fármacos , Cinética , Lactose , Meloxicam/química , Nanoestruturas , Tamanho da Partícula , Solubilidade , Tensoativos , Suspensões
20.
AAPS PharmSciTech ; 21(5): 158, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32458106

RESUMO

The relationship between the geometric particle size distribution (GPSD) and the aerodynamic particle size distribution (APSD) of commercial solution and suspension metered-dose inhaler (MDI) formulations was assessed to clarify the use of GPSD to estimate the APSD. The size distribution of particles discharged from four suspension and four solution MDIs was measured using the Inas®100 light-scattering spectrometer and a Next Generation Impactor. The conversion factor was calculated by measuring the GPSD and APSD of MDIs. The morphology and physical properties of MDIs were studied using scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). Six of the eight MDIs showed similar conversion factor profiles, irrespective of their composition and formulation types. Applying the conversion factor obtained from one of the six MDIs resulted in a particle size distribution comparable to each APSD except for some formulations. The two other solution MDIs, which contained citric acid, had much higher and variable conversion factors. SEM images and DSC scans of the solids obtained by nebulization of the solutions containing beclomethasone and/or citric acid showed the formation of a paste-like amorphous solid. These results indicated that APSD of solution and suspension MDIs that form rigid particles may be estimated by using the conversion factor and GPSD. Contrarily, the estimation is more difficult in formulations that tend to lose the particle structure during the measurement.


Assuntos
Inaladores Dosimetrados , Tamanho da Partícula , Administração por Inalação , Aerossóis/química , Beclometasona/química , Nebulizadores e Vaporizadores , Soluções , Suspensões
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