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Na área da saúde pública, as doenças provocadas pela radiação solar têm ganho grande destaque, por serem cada vez mais comuns. Dentre as principais formas de prevenção a utilização de filtros solares são as mais comuns e de fácil acesso. Os filtros utilizados atuam por sua capacidade de refletir, absorver ou dispersar os raios solares ultravioletas (UV). A aplicação de métodos teóricos tornou-se indispensável no auxílio do planejamento de novos compostos com função terapêutica, em estudos de suas diferentes propriedades, buscando gerar, manipular e analisar representações realistas de estruturas moleculares obtidas a partir de cálculos de propriedades físico-químicas por meio da química computacional. Neste estudo, foram selecionados compostos naturais de origem vegetal (3-O-metilquercetina, ácido gálico, aloína, catequina, quercetina e resveratrol), os quais são descritos com propriedades fotoprotetoras, para os quais se aplicou métodos computacionais para predição dos espectros de absorção, por meio do método TD-DFT (Teoria funcional da densidade dependente do tempo). Foram avaliadas as principais transições eletrônicas dos compostos estudados e se as diferenças de energia HOMO e LUMO para os compostos que absorvem na faixa UV compreendem na UVA (320400 nm, 3.103.87 eV), UVB (290320 nm, 3.874.27 eV) ou na UVC (100290 nm, 4.2712.4 eV). Realizou-se a validação experimental para o método aplicado para o EMC, quercetina e resveratrol, demonstrando a eficácia. Após os estudos realizados concluímos que o resveratrol, teoricamente é um ótimo candidato a fotoprotetor. O estudo ofereceu informações relevantes sobre o poder de predição in silico para fotoprotetores, e se utilizado pode contribuir diminuindo de tempo e custos em pesquisas para desenvolver fármacos
In the area of public health, diseases caused by solar radiation have gained great prominence, as they are increasingly common. Among the main ways to prevent the use of sunscreens are the most common and easily accessible. The filters used act by their ability to reflect, absorb or scatter the sun's ultraviolet (UV) rays. The application of theoretical methods has become indispensable in helping to plan new compounds with therapeutic function, in studies of their different properties, seeking to generate, manipulate and analyze realistic representations of molecular structures obtained from calculations of physicochemical properties through computational chemistry. In this study, natural compounds of plant origin (3-O-methylquercetin, gallic acid, aloin, catechin, quercetin, and resveratrol) were selected, which are described with photoprotective properties, for which computational methods were applied to predict the absorption spectra, using the TD-DFT (Time-Dependent Density Functional Theory) method. The main electronic transitions of the studied compounds were evaluated and whether the differences in HOMO and LUMO energy for compounds that absorb in the UV range comprise UVA (320400 nm, 3.103.87 eV), UVB (290 320 nm, 3.87 4.27 eV) or UVC (100290 nm, 4.2712.4 eV). Experimental validation was carried out for the method applied for CME, quercetin, and resveratrol, demonstrating its effectiveness. After the studies carried out, we concluded that resveratrol, theoretically, is an excellent candidate for sunscreen. The study provided relevant information about the in silico predictive power for photoprotectors, and if used, it can contribute to reducing time and costs in research to develop drugs
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Sunscreening Agents/analysis , Biological Products/adverse effects , Pharmaceutical Preparations/analysis , Ultraviolet Filters , Sun Protection Factor/instrumentation , Ultraviolet Rays/adverse effects , Molecular Structure , Solar Radiation , Density Functional TheoryABSTRACT
Objective: To compare the prognostic factors of mortality among melioidosis patients between lognormal accelerated failure time (AFT), Cox proportional hazards (PH), and Cox PH with timevarying coefficient (TVC) models. Methods: A retrospective study was conducted from 2014 to 2019 among 453 patients who were admitted to Hospital Sultanah Bahiyah, Kedah and Hospital Tuanku Fauziah, Perlis in Northern Malaysia due to confirmed-cultured melioidosis. The prognostic factors of mortality from melioidosis were obtained from AFT survival analysis, and Cox s models and the findings were compared by using the goodness of fit methods. The analyses were done by using Stata SE version 14.0. Results: A total of 242 patients (53.4%) survived. In this study, the median survival time of melioidosis patients was 30.0 days (95% CI 0.0-60.9). Six significant prognostic factors were identified in the Cox PH model and Cox PH-TVC model. In AFT survival analysis, a total of seven significant prognostic factors were identified. The results were found to be only a slight difference between the identified prognostic factors among the models. AFT survival showed better results compared to Cox's models, with the lowest Akaike information criteria and best fitted Cox-snell residuals. Conclusions: AFT survival analysis provides more reliable results and can be used as an alternative statistical analysis for determining the prognostic factors of mortality in melioidosis patients in certain situations.
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Objective To analyze the global status of COVID-19 epidemics, so as to preliminarily forecast the epidemic trend. Methods The epidemiological data of 208 countries and the prevention and control policies implemented by typical countries from December 31, 2019 to December 14, 2020 were collected. We use the cumulative incidence rate, cumulative mortality, cumulative fatality and real-time dependent reproduction number (Rt) to analyze the epidemic status. We use the provenance package to group different countries and discuss the effect of prevention and control measures. Results As of December 14, 2020, a cumulative incidence of 93.49 per 10000, a cumulative mortality rate of 0.21‰, and a cumulative fatality rate of 3.1‰ had been reported globally.112 of the 208 countries still had Rt ≥ 1.0, and 96 countries had Rt t , and the government had adopted more relaxed epidemic prevention measures. The epidemic situation in this region may continue to deteriorate, and needs to be focused in the later period.
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Objective:To study the influence of time-dependent acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score on 14-day death risk in patients with severe stroke, and to provide reference for clinical diagnosis and treatment.Methods:Data of 3 229 patients with severe stroke were enrolled from Medical Information Mart for Intensive Care-Ⅲ (MIMIC-Ⅲ). According to the main types of stroke, the patients were divided into subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), ischemic stroke (IS) and other groups. According to age, patients were divided into > 60 years old and ≤ 60 years old subgroups. According to the baseline of sequential organ failure assessment (SOFA) score, they were divided into subgroups of > 3 and ≤ 3. The daily measured values of APACHE Ⅱ scores in each patient were recorded. And all-cause death within 14 days after admission to intensive care unit (ICU) was used as the outcome index to obtain the survival status and survival time of patients. Joint models for longitudinal and time-to-event data were established to evaluate the effect of APACHE Ⅱ score measured at multiple time points on the death risk of patients, and a subgroup analysis was performed.Results:Among the joint models, the one which include APACHE Ⅱ score, and the interaction items between APACHE Ⅱ and age showed the better fitting. Further analysis showed that APACHE Ⅱ score was affected by age, gender, hospital admission, baseline SOFA score and smoking history. After controlling for these confounding factors, APACHE Ⅱ score was significantly associated with 14-day all-cause death in patients with severe stroke [hazard ratio ( HR) = 1.48, 95% confidence interval (95% CI) was 1.31-1.66, P < 0.001], which indicated that the risk of death increased by 48% (95% CI was 31%-66%) for each 1-point increase in APACHE Ⅱ score. Subgroup analysis showed that for different types of severe stroke patients, APACHE Ⅱ score had a greater impact on the risk of 14-day death in SAH patients ( HR = 1.43, 95% CI was 1.10-1.85), but had a smaller impact on ICH and IS groups [HR (95% CI) was 1.37 (1.15-1.64) and 1.35 (1.06-1.71), respectively]. There was no significant difference in APACHE Ⅱ score on the risk of 14-day death between the patients aged > 60 years old and those aged ≤ 60 years old [ HR (95% CI): 1.37 (1.08-1.72) vs. 1.35 (1.07-1.70), respectively]. Compared with patients with SOFA score > 3, APACHE Ⅱ score had a greater impact on the risk of 14-day death in patients with SOFA score ≤ 3 [ HR (95% CI): 1.40 (1.16-1.70) vs. 1.34 (1.16-1.55)]. Conclusion:Time-dependent APACHE Ⅱ score is an important indicator to evaluate the risk of death in patients with severe stroke.
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In prospective cohort study, multi follow up is often necessary for study subjects, and the observed values are correlated with each other, usually resulting in time-dependent confounding. In this case, the data generally do not meet the application conditions of traditional multivariate regression analysis. Sequential conditional mean model (SCMM) is a new approach that can deal with time-dependent confounding. This paper mainly summarizes the basic theory, steps and characteristics of SCMM.
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OBJECTIVE: To compare and evaluate different methods of estimating %T>MIC based on drug concentration monitoring data, and clarify the implementation plan and treatment objectives of therapeutic drug monitoring. METHODS: The plasma drug concentrations of 25 patients with severe infections were collected at multiple time points after imipenem reached steady state. A population pharmacokinetic model was established by NONMEM method. The plasma drug concentrations were estimated by Bayesian feedback method at 6 and 8 h after imipenem administration. Meanwhile, the established calculation model of %T>MIC combined with the same drug concentrations was used to estimate the %T>MIC. The results of these two methods were compared with the true value of %T>MIC. RESULTS: The established population pharmacokinetic model could fit the data well. The covariate serum creatinine (CR) had a significant effect on the apparent distribution volume (Vc) of central ventricle. The final model was Vc=18.8×(CR/70.9)ΘCR_VC. When MIC=2, the results of Bayesian method and %T>MIC calculation model method showed 76.9% and 84.6% deviation within±10% of the true values, respectively. CONCLUSION: The two methods had good predictive accuracy when the MIC breakpoint was less than 2, but they decreased with the increase of MIC. Different therapeutic drug monitoring schemes should be considered for different levels of MIC.
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In prospective cohort study, multi follow up is often necessary for study subjects, and the observed values are correlated with each other, usually resulting in time-dependent confounding. In this case, the data generally do not meet the application conditions of traditional multivariate regression analysis. Sequential conditional mean model (SCMM) is a new approach that can deal with time-dependent confounding. This paper mainly summarizes the basic theory, steps and characteristics of SCMM.
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As a follow-up to a previous article, this review provides several in-depth concepts regarding a survival analysis. Also, several codes for specific survival analysis are listed to enhance the understanding of such an analysis and to provide an applicable survival analysis method. A proportional hazard assumption is an important concept in survival analysis. Validation of this assumption is crucial for survival analysis. For this purpose, a graphical analysis method and a goodness-of-fit test are introduced along with detailed codes and examples. In the case of a violated proportional hazard assumption, the extended models of a Cox regression are required. Simplified concepts of a stratified Cox proportional hazard model and time-dependent Cox regression are also described. The source code for an actual analysis using an available statistical package with a detailed interpretation of the results can enable the realization of survival analysis with personal data. To enhance the statistical power of survival analysis, an evaluation of the basic assumptions and the interaction between variables and time is important. In doing so, survival analysis can provide reliable scientific results with a high level of confidence.
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Humans , Follow-Up Studies , Methods , Proportional Hazards Models , Statistics as Topic , Survival AnalysisABSTRACT
OBJECTIVE: To develop the f%T>MIC computing model of carbapenems and adjust dose strategy based on the drug concentrations. METHODS: Pharmacokinetic equations within one time interval were deduced at steady state after multiple intravenous infusion. f%T>MIC calculator was compiled using EXCEL software and used for evaluation of antibiotic effect based on the concentrations at 0.5 and 3 h before administration of imipenem or meropenem at steady state. RESULTS: The calculation model can be used for f%T>MIC evaluation and dosage optimization. The model was used to determine f%T>MIC level of 107 ICU patients receiving imipenem or meropenem treatment. CONCLUSION: The present calculation model can provide a basis for the evaluation and optimization of dosage strategy,and it can be applied to other time-dependent antibiotics.
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In the studies of modem epidemiology,exposure in a short term cannot fully elaborate the mechanism of the development of diseases or health-related events.Thus,lights have been shed on to life course epidemiology,which studies the exposures in early life time and their effects related to the development of chronic diseases.When exploring the mechanism leading from one exposure to an outcome and its effects through other factors,due to the existence of time-variant effects,conventional statistic methods could not meet the needs of etiological analysis in life course epidemiology.This paper summarizes the dynamic path analysis model,including the model structure and significance,and its application in life course epidemiology.Meanwhile,the procedure of data processing and etiology analyzing were introduced.In conclusion,dynamic path analysis is a useful tool which can be used to better elucidate the mechanisms that underlie the etiology of chronic diseases.
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In the studies of modem epidemiology,exposure in a short term cannot fully elaborate the mechanism of the development of diseases or health-related events.Thus,lights have been shed on to life course epidemiology,which studies the exposures in early life time and their effects related to the development of chronic diseases.When exploring the mechanism leading from one exposure to an outcome and its effects through other factors,due to the existence of time-variant effects,conventional statistic methods could not meet the needs of etiological analysis in life course epidemiology.This paper summarizes the dynamic path analysis model,including the model structure and significance,and its application in life course epidemiology.Meanwhile,the procedure of data processing and etiology analyzing were introduced.In conclusion,dynamic path analysis is a useful tool which can be used to better elucidate the mechanisms that underlie the etiology of chronic diseases.
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ABSTRACT The aim of this study was to formulate and prepare compression-coated tablets for colonic release (CR-tablets), and to evaluate the bioavailability of ketoprofen following the administration of a single dose from mini-tablets with immediate release (IR-tablets) compared to CR-tablets. CR-tablets were prepared based on time-controlled hydroxypropylmethylcellulose K100M inner compression-coating and pH-sensitive Eudragit® L 30D-55 outer film-coating. The clinical bioavailability study consisted of two periods, in which two formulations were administered to 6 volunteers, according to a randomized cross-over design. The apparent cumulative absorption amount of ketoprofen was estimated by plasma profile deconvolution. CR-tablets were able to delay ketoprofen's release. Compared to IR-tablets used as reference, for the CR-tablets the maximum plasma concentration (Cmax) was lower (4920.33±1626.71 ng/mL vs. 9549.50±2156.12 ng/mL for IR-tablets) and the time needed to reach Cmax (tmax) was 5.33±1.63 h for CR-tablets vs. 1.33±0.88 h for IR-tablets. In vitro-in vivo comparison of the apparent cumulative absorption amount of ketoprofen showed similar values for the two formulations. Therefore, the obtained pharmacokinetic parameters and the in vitro-in vivo comparison demonstrated the reliability of the developed pharmaceutical system and the fact that it is able to avoid the release of ketoprofen in the first part of the digestive tract.
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Humans , Adult , Tablets/analysis , Ketoprofen/administration & dosageABSTRACT
Objective Nomilin and obacunone are two important limonoids that are well known for their anticancer effect. Previous studies showed that limonoids had inhibitory effect on cytochrome P450 3A4 (CYP3A4). However these effects are inconclusive with regards to prediction of potential drug interactions. Methods Nomilin or obacunone was pre-incubated with HLMs for 30 min. Following 10-fold dilution from the pre-incubation concentration, a second incubation was performed in the presence of NADPH and cytochrome P450 substrates for 15 min. The reaction was quenched and the supernatants were analyzed by chromatography/mass spectrometry. Results In this study, nomilin and obacunone showed potent inhibitory effect on CYP3A4 with the IC50 values of 3.50 and 6.08 µmol/L, respectively. The inhibition of CYP3A4 was in a time-, concentration- and NADPH-dependent manner with Ki values of 2.92 and 1.25 µmol/L and Kinact values of 0.033 and 0.078 min−1 for nomilin and obacunone respectively. These results elucidated that they were time-dependent inhibitors for CYP3A4. Conclusion Concomitant use of limonoids and other drugs may call for extra caution for purposes of clinical safety.
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Objective To study the prognostic factors of operative patients with colorectal cancer.Methods Four hundreds and ninety-four patients with colorectal cancer treated from January 2003 to December 2009 in Shanxi Cancer Hospital were involved in this study.The demographic data,clinical and pathological features,serum levels of tumor markers were analyzed retrospectively.The prognostic factors were analyzed by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazards models.Results The 1-,2-,3-,4-,5-year survival rates of 494 patients were 92.31％,69.43 ％,50.00 ％,31.17 ％ and 12.96 ％ respectively.Non-Cox proportional hazards model with time-according to coefficient of multivariate analysis showed that Duke stage,tumor metastasis,pathological diagnosis and serum carcinocmbryonic antigen (CEA) levels were the prognostic factors of colorectal cancer.Conclusion The Duke stage,tumor metastasis,pathological diagnosis and CEA levels are the prognostic factors of colorectal cancer,which should be considered in the choice of clinical treatment and prognosis judgement.
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Objective To identify the risk factors associated with cardiovascular and cerebrovascular disease (CCVD) in maintenance hemodialysis (MHD) patients. Methods We analyzed all of the patients undergoing maintenance hemodialysis in the dialysis center of the 3rd Affiliated Hospital of Sun Yat-sen University for at least 3 months from Jan 1st, 2009 to Dec 31st, 2014. Baseline and yearly interval clinical data were recorded and patients were followed up until morbidity or death of CCVD. Cox proportional hazard regression and time-dependent Cox regression were used to estimate the relative risk of outcomes associated with clinical measurements. Results There were 243 patients enrolled in the study, with a mean age of (53.2 ± 16.4) years old, and 138 of them were male (56.8%). The multivariate Cox proportional model revealed that age (HR=1.040, 95%CI:1.015-1.065, P=0.002), Erythropoietin (EPO) dose (HR=0.914, 95%CI: 0.846-0.987, P=0.022) and history of cardiovascular and cerebrovascular disease (HR=4.045, 95%CI: 2.074-7.890, P<0.001) were independent predictors of CCVD in MHD patients. After adjusting for baseline predictors, time-dependent serum phosphorus level (HR=1.722, 95%CI: 1.034-2.866, P=0.037) was significantly associated with CCVD. Conclusion Older age, decreases in EPO dose and history of cardiovascular and cerebrovascular disease were associated with increased risks of CCVD in MHD patients. Increase in serum phosphorus level was associated with increased risks of CCVD in a time-dependent manner.
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Decalcification and its effect on microhardness of root canal dentin by an aqueous solution of 17% EDTA at different time intervals were studied.Single rooted forty extracted human premolar teeth after adequate processing and embedded with acrylic resin were randomly divided into 8 groups based on different time intervals. Each sample group was assessed for Ca<sup>2+</sup> release into the test solution by Atomic Absorption Spectrophotometer, respectively and then were subjected for microhardness testing.17% EDTA and 0.9% Saline, test solutions were used; EDTA was adjusted to 7.5 pH. Data analysis was done by One Way analysis of variance (ANOVA) and the comparison of means was done by using Tukey’s multiple comparison tests. The decalcifying activity of 17% EDTA solution was time dependent and increased immersion time showing very high significant influence on the amount of calcium extracted (<strong>F=154.304, p). The reduction in microhardness for 17% EDTA solution was time dependent and increased immersion time showing very high significant decrease in the microhardness among the different time intervals tested (<strong>F=249.925, p < 0.0005</strong>).Effect of 17 % EDTA solution as root canal irrigant is time dependent as evidenced by dentin microhardness reduction.
Subject(s)
Calcium , Dental Pulp Cavity/drug effects , Dental Pulp Cavity/pharmacology , Dentin/drug effects , Dentin/pharmacology , Edetic Acid/analogs & derivatives , Edetic Acid/therapeutic use , Hardness , Hardness Tests , Humans , Spectrum Analysis , Time FactorsABSTRACT
Phthiobuzone is a bis(thiosemicarbazone) derivative with a single chiral center which has been used as a racemate in the clinical treatment of herpes and trachoma diseases. In this study, its two enantiomers were prepared from chiral amino acids and their absolute configurations were investigated by electronic circular dichroism (ECD) combined with modern quantum-chemical calculations using time-dependent density functional theory. It was found that solvation changed both the conformational distribution and the ECD spectrum of each conformer. The theoretical ECD spectra of the two enantiomers were in good agreement with the experimentally determined spectra of the corresponding isomers in dimethyl sulfoxide. The ECD behavior of the bis(thiosemicarbazone) chromophore in a chiral environment is also discussed. Our results indicate that ECD spectroscopy may be a useful tool for the stereochemical evaluation of chiral drugs.
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OBJECTIVE: To estimate and optimize the dosing regimens of antibiotics in general surgery with the utilization of Monte Carlo simulation (MCS) based on PK/PD. METHODS: The mean treatment duration(MTD) of different dosing regimens were gathered from clinical cases. MCS model was used to simulate the regimens against Escherichia coli, Klebsiella pneumonius, Acinetobacter baumannii and Pseudomonas aeruginosa, respectively. RESULTS: The CFRs of 500 mg TID, 500 mg QID, 1.0 g BID and 1.0 g TID imipenem against Escherichia coli and Klebsiella pneumonius were greater than that of 500 mg BID (100%; 99%). Correspondingly, MTD of those regimens achieved CFR 100% were shorter than that of 500 mg BID. The CFRs of imipenem against Acinetobacter baumannii and Pseudomonas aeruginosa were all less than 90%, the CFRs of 200 mg BID, 400 mg QD levofloxacin and 200 mg QD, 200 mg BID, 400 mg QD amikacin were all below 90%. CONCLUSION: The 5 dosing regimens of imipenem were all effective against Escherichia coli and Klebsiella pneumonius. In consideration of pharmaceutical economics, 500 mg TID was the most rational choice. It suggested drug resistance and promoted combined medication that the CFRs of imipenem against Acinetobacter baumannii and Pseudomonas aeruginosa failed to achieve 90%. Drug resistance was also demonstrated by low CFR values of levofloxacin and amikacin treatments. Nevertheless, results of MCS showed inversely proportional between MTD and CFRs, and displayed obvious dose-dependent characteristics of levofloxacin and amikacin. On the purpose of achieving effective concentration, sufficient dose once a day of levofloxacin and amikacin medication were recommend.
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Now days natural polysaccharides are extensively used for the development of solid dosage forms for delivery of drug to the colon. The objective of the present study was to develop a site-specific drug, single unit formulation allowing targeted drug release in the colon. Solid unit dosage forms were prepared using polysaccharides or synthetic polymer included xanthan gum, pectin, chitosan and Eudragit-E. Meloxicam was used as a model drug. The prepared tablets were enteric coated with Eudragit-S 100 to give protection in the stomach. The coated tablets were tested in-vitro for their suitability as colon specific drug delivery systems. The dissolution data so obtained illustrates that enteric coated tablets containing 3% chitosan as a binder, showed only 12.5% drug release in the first 5 h, which is the usual upper gastrointestinal transit time, whereas, tablets prepared using xanthan gum as binder, were unable to protect drug release under similar conditions. Solid formulations containing pectin as a binder formed time-dependent release formulations. 28% drug release was observed in the usual upper gastrointestinal tract conditions, when used in a concentration of 5.92% in the tablets.
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The aim of present study was the assessment of antimicrobial activity of prepared time-dependent release bilayer tablets of amoxicillin trihydrate and in vitro evaluation of drug release by antimicrobial assay using agar plate diffusion method. The bilayer tablets comprised of a delayed and sustained release layer. Direct compression method was used for the preparation of bilayer tablets containing Eudragit-L100 D55 as delayed release polymer, and HPMCK4M and HPMCK15 as sustained release polymers. The prepared bilayer tablets containing amoxicillin trihydrate were evaluated for hardness, thickness, friability, weight variation and drug content. Further, in vitro drug release was assessed by antimicrobial assay using S. aureus and E. coli as test microorganisms. The aliquot samples of in vitro drug release study were found to be effective against both microorganisms for 16 hours due to sustained action. The in vitro drug release study and antimicrobial assay showed that bilayer tablets have sustained release profile of drug delivery with time-dependent burst release after a lag-time of 2 hours. The lower MIC value (2 µg/mL) of prepared bilayer tablets vis-à-vis marketed preparation (5 µg/mL) represented its good antimicrobial activity.
O objetivo do presente estudo foi avaliar a atividade antimicrobiana de formulações de comprimidos de dupla camada contendo amoxicilina triidratada para liberação tempo dependente e avaliação da liberação in vitro do fármaco pelo ensaio de atividade antimicrobiana utilizando o método de difusão em placa de ágar. Os comprimidos de dupla camada consistem em uma camada para liberação retardada e outra sustentada. O método de compressão direta foi usado para a preparação dos comprimidos de dupla camada contendo Eudragit-L 100 D55 como polímero para liberação retardada e HPMCK4M ou HPMCK15 como polímeros para liberação sustentada. As formulações de comprimidos de dupla camada contendo amoxicilina triidratada foram avaliadas quanto a dureza, espessura, friabilidade, variação de peso e conteúdo de fármaco. Além disso, a liberação do fármaco in vitro foi avaliada por ensaio de atividade antimicrobiana usando S. aureus e E. coli como microrganismos teste. A alíquota das amostras do estudo de liberação do fármaco in vitro demonstrou ser efetiva contra ambos os microrganismos por um período de 16 horas devido à ação sustentada. O estudo de liberação do fármaco in vitro e o ensaio de atividade antimicrobiana mostraram que os comprimidos de dupla camada tiveram um perfil de liberação sustentada do fármaco com um pico de liberação após 2 horas de ensaio. O menor valor de MIC (2 ug/mL) dos comprimidos de dupla camada quando comparados à formulação comercial (5 ug/mL) representa uma boa atividade antimicrobiana.