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In an end-to-end authentication (E2EA) scheme, the physician, patient, and sensor nodes authenticate each other through the healthcare service provider in three phases: the long-term authentication phase (LAP), short-term authentication phase (SAP), and sensor authentication phase (WAP). Once the LAP is executed between all communication nodes, the SAP is executed (m) times between the physician and patient by deriving a new key from the PSij key generated by healthcare service provider during the LAP. In addition, the WAP is executed between the connected sensor and patient (m + 1) times without going back to the service provider. Thus, it is critical to determine an appropriate (m) value to maintain a specific security level and to minimize the cost of E2EA. Therefore, we proposed an analytic model in which the authentication signaling traffic is represented by a Poisson process to derive an authentication signaling traffic cost function for the (m) value. wherein the residence time of authentication has three distributions: gamma, hypo-exponential, and exponential. Finally, using the numerical analysis of the derived cost function, an optimal value (m) that minimizes the authentication signaling traffic cost of the E2EA scheme was determined.
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Redes de Comunicación de Computadores , Seguridad Computacional , Algoritmos , Comunicación , HumanosRESUMEN
Single-photons with high spectro-temporal purity are an essential resource for quantum photonic technologies. The highest reported purity up until now from a conventional silicon photonic device is 92% without any spectral filtering. We have experimentally generated and observed single-photons with 98.0±0.3% spectro-temporal purity, an upper bound of the stimulated emission tomography, using a conventional micro-racetrack resonator and an engineered dual pump pulse.
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OBJECTIVE: To study the potential influence of selected metal ions on absorption (and hence oral bioavailability of ciprofloxacin (Cipro) in presence and absence of a competing ligand. SIGNIFICANCE: The presence of metal ions together with Cipro results in complexes exhibiting a decreased bioavailability. Attempts were made to better understand the mechanism of decreased Cipro bioavailability in the presence of metals such as calcium and ferrous ions, and a small-sized ligand citric acid (CitA). METHODS: Effect of complex size or other potential factors was studied using diffusion through synthetic membrane, permeation studies across Caco-2 cells and capillary electrophoresis. A molecular dynamics (MD) simulation study was conducted to find the arrangement and the nature of the interactions between Cipro molecules and ferrous ions. RESULTS: Cipro was shown to form complexes with metals and CitA. The presence of CitA improved permeation of Cipro through the synthetic membrane but this was not as obvious in case of Caco-2 cells. Capillary electrophoresis suggested the existence of large molecular aggregates of Cipro: metal complexes. MD simulations offered clear evidence of large size aggregates in line with the experimental findings. CitA alone significantly improved permeation of Cipro through Caco-2 cells. CONCLUSIONS: The size of the formed complexes, rather than the decrease in the solubility of formed complexes, plays a significant role in permeation (absorption) of Cipro. CitA might ameliorate the effect of co-administered metal ions on the bioavailability of Cipro.
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Antiinfecciosos/farmacocinética , Calcio/farmacología , Ciprofloxacina/farmacocinética , Ácido Cítrico/farmacología , Compuestos Ferrosos/farmacología , Absorción Intestinal/efectos de los fármacos , Antiinfecciosos/administración & dosificación , Disponibilidad Biológica , Células CACO-2 , Permeabilidad de la Membrana Celular , Ciprofloxacina/administración & dosificación , Difusión , Electroforesis Capilar , Humanos , Iones , Solubilidad , Espectrofotometría UltravioletaRESUMEN
High visibility on-chip quantum interference among indistinguishable single-photons from multiples sources is a key prerequisite for integrated linear optical quantum computing. Resonant enhancement in micro-ring resonators naturally enables brighter, purer and more indistinguishable single-photon production without any tight spectral filtering. The indistinguisha-bility of heralded single-photons from multiple micro-ring resonators has not been measured in any photonic platform. Here, we report on-chip indistinguishability measurements of heralded single-photons generated from independent micro-ring resonators by using an on-chip Mach-Zehnder interferometer and spectral demultiplexer. We measured the raw heralded two-photon interference fringe visibility as 72 ± 3%. This result agrees with our model, which includes device imperfections, spectral impurity and multi-pair emissions. We identify multi-pair emissions as the main factor limiting the nonclassical interference visibility, and show a route towards achieving near unity visibility in future experiments.
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BACKGROUND: Robust data on quality of life (QoL) after different techniques of bariatric surgery are sparse. This RCT compared excess weight loss (EWL) and QoL after sleeve gastrectomy versus Roux-en-Y gastric bypass (RYGB). METHODS: Obese patients were assigned randomly to RYGB or sleeve gastrectomy. The primary outcome measure was EWL. Secondary outcomes included QoL, co-morbidity, adverse events, vitamin and glycolipid status. QoL was assessed before and annually after surgery, using the Moorehead-Ardelt Quality of Life Questionnaire II (M-A-QoLQII) and Gastrointestinal Quality of Life Index (GIQLI). RESULTS: One hundred patients were enrolled, 45 in the RYGB group and 55 in the sleeve gastrectomy group. Mean postoperative EWL at 1, 2, 3 and 5 years was 80·4, 79·8, 83·0 and 74·8 per cent respectively after RYGB, and 83·0, 77·8, 66·3 and 65·1 per cent after sleeve gastrectomy (P = 0·017). Mean M-A-QoLQII score before surgery and at 1, 2, 3 and 5 years after operation was 0·5, 1·6, 1·7, 2·1 and 1·4 respectively after RYGB, and 0·3, 1·7, 1·5, 1·5 and 1·2 after sleeve gastrectomy. Mean GIQLI score before and at 1, 2, 3, 5 years after RYGB was 96·4, 113·8, 113·3, 113·4, 111·7, compared with 90·7, 113·9, 114·5, 113·1 and 113·0 for sleeve gastrectomy. The improvement was significant compared with preoperative values (P < 0·001 for M-A-QoLQII and GIQLI), with no difference between groups (P = 0·418 and P = 0·323 respectively). RYGB resulted in higher readmission rates (P = 0·002) and length of hospital stay (P = 0·006) than sleeve gastrectomy. CONCLUSION: RYGB and sleeve gastrectomy resulted in equivalent, long-standing QoL improvement. RYGB resulted in more stable weight loss but was associated with higher readmission rates. Registration number: NCT02475590.
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Gastrectomía , Derivación Gástrica , Obesidad Mórbida/cirugía , Calidad de Vida , Pérdida de Peso , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Gastrectomía/métodos , Derivación Gástrica/métodos , Indicadores de Salud , Humanos , Laparoscopía , Masculino , Persona de Mediana Edad , Readmisión del Paciente/estadística & datos numéricos , Resultado del Tratamiento , Adulto JovenRESUMEN
AIMS: To examine the association between low 25-OH Vitamin D levels and prevalence of advanced adenomas (AAs) in screening/surveillance colonoscopy patients. RATIONALE: Low serum 25-OH Vitamin D has been associated with an increased risk for colon cancer. In the Adenoma-Carcinoma pathway, a subset of colon polyps (AA) have been regarded as high-risk precursor lesions. We used a retrospective case-control design to examine the association between Vitamin D deficiency and the prevalence of AA in a high-risk population. MATERIALS AND METHODS: We examined a total of 354 patients who presented for initial screening or surveillance colonoscopy at our Colon Cancer Prevention Program. Our main exposure variable was serum Vitamin D levels and the outcome was AAs defined as those adenomas that were large (≥1 cm) or had advanced pathology (>25% villous components or high-grade dysplasia). Known risk factors were also collected from the patients' charts including gender, age, smoking, and family history. Bivariate and multivariate analyses were performed to examine the relationship between serum 25-OH Vitamin D levels and AAs. A total of 354 patients [(males, 188; females, 166); average age, 61 y] charts were reviewed. Vitamin D levels ranged between 4 and 70 ng/mL, with a mean of 25 ng/mL (clinical laboratory normal>30 ng/mL). There was no significant association between serum levels and time of the year of blood draw. Risk for tubular adenoma and AA increased as Vitamin D levels decreased to <30 ng/mL (P=0.002). In total, 80% of AAs were detected in patients whose levels were below this value (odds ratio, 3.36; 95% confidence interval, 1.40-8.03; P=0.007). Bivariate analysis also showed a positive association between smokers with AA as well as those with a family history of colon cancer (P=0.011) and low Vitamin D levels (P=0.001). A multivariate analysis using quintiles of Vitamin D levels demonstrated an increased risk of AAs for patients with levels in the second quintile (33 ng/mL) (odds ratio, 4.3; P=0.01) MAIN CONCLUSIONS:: Most patients presenting in our Colon Cancer Prevention Program have low levels of serum 25-OH Vitamin D. Analysis of the results of both screening and surveillance colonoscopies demonstrated an inverse relation between serum 25-OH Vitamin D level and AAs.
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Adenoma/etiología , Neoplasias del Colon/etiología , Deficiencia de Vitamina D/complicaciones , Vitamina D/análogos & derivados , Adenoma/diagnóstico , Adenoma/patología , Anciano , Biomarcadores de Tumor/sangre , Estudios de Casos y Controles , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/patología , Pólipos del Colon/patología , Colonoscopía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Vitamina D/sangreRESUMEN
Complexes of diclofenac sodium (DF-Na) with hydroxypropyl betacyclodextrin (HPßCD) were prepared by co-evaporation in a 1:1 ratio and characterized in light of previously reported data. Phase solubility diagrams were obtained for DF-Na with HPßCD in the presence and absence of zinc ions. Dissolution profiles were obtained for DF-Na and its HPßCD complex at acidic (pH 1.2) as well as in phosphate buffer (pH 6.8), in the presence and absence of zinc. HPßCD, as expected, was shown to improve the dissolution of DF-Na in acidic medium but not in phosphate buffer (pH 6.8). The presence of zinc ions decreased the in vitro dissolution of DF-HPßCD complex in acidic medium (pH 1.2) but not in phosphate buffer (pH 6.8). It was confirmed that the precipitate that was formed by zinc ions in the presence of HPßCD and DF-Na contained no cyclodextrin and most likely it was a mixture of the complexes: DF2-Zn and DF-Zn with some molecules of water. In vivo experiments on rats have shown that HPßCD has no statistically significant effect on absorption or bioavailability of DF-Na in spite of the observed improvement of its in vitro dissolution by HPßCD. Moreover, zinc ions were shown to decrease the absorption rate of DF-Na in rats model but did neither significantly alter the absorption nor bioavailability of DF-HPßCD complex. The zinc induced precipitates of DF were shown to have significantly different crystalline properties when HPßCD was present. Therefore, the pharmaceutical details of a DF-Na preparation should be considered when designing the formulation and predicting possible interaction between DF-Na (or other potential NSAIDs) and zinc metal.
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Antiinflamatorios no Esteroideos/farmacología , Diclofenaco/farmacología , Zinc/farmacología , beta-Ciclodextrinas/farmacología , Animales , Disponibilidad Biológica , Rastreo Diferencial de Calorimetría , Diclofenaco/farmacocinética , Combinación de Medicamentos , Interacciones Farmacológicas , Ratas , Ratas Sprague-Dawley , Espectroscopía Infrarroja por Transformada de Fourier , beta-Ciclodextrinas/farmacocinéticaRESUMEN
Complexes of diclofenac sodium (DF-Na) with hydroxypropyl betacyclodextrin (HPßCD) were prepared by co-evaporation in a 1:1 ratio and characterized in light of previously reported data. Phase solubility diagrams were obtained for DF-Na with HPßCD in the presence and absence of zinc ions. Dissolution profiles were obtained for DF-Na and its HPßCD complex at acidic (pH 1.2) as well as in phosphate buffer (pH 6.8), in the presence and absence of zinc. HPßCD, as expected, was shown to improve the dissolution of DF-Na in acidic medium but not in phosphate buffer (pH 6.8). The presence of zinc ions decreased the in vitro dissolution of DF-HPßCD complex in acidic medium (pH 1.2) but not in phosphate buffer (pH 6.8). It was confirmed that the precipitate that was formed by zinc ions in the presence of HPßCD and DF-Na contained no cyclodextrin and most likely it was a mixture of the complexes: DF2-Zn and DF-Zn with some molecules of water. In vivo experiments on rats have shown that HPßCD has no statistically significant effect on absorption or bioavailability of DF-Na in spite of the observed improvement of its in vitro dissolution by HPßCD. Moreover, zinc ions were shown to decrease the absorption rate of DF-Na in rats model but did neither significantly alter the absorption nor bioavailability of DF-HPßCD complex. The zinc induced precipitates of DF were shown to have significantly different crystalline properties when HPßCD was present. Therefore, the pharmaceutical details of a DF-Na preparation should be considered when designing the formulation and predicting possible interaction between DF-Na (or other potential NSAIDs) and zinc metal.
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Ciclodextrinas/química , Ciclodextrinas/farmacocinética , Diclofenaco/química , Diclofenaco/farmacocinética , Zinc/química , Zinc/farmacocinética , Animales , Química Farmacéutica , Iones , Ratas , Ratas Sprague-DawleyRESUMEN
The interaction of pharmacologically active drugs with SC biochemical components is underestimated in pharmaceutical research. The aim of this research was to illustrate that some drugs intended for transdermal delivery could interact with the protein component of SC. Such interactions could be in favor of or opposition to their percutaneous absorption. IR microspectroscopy was used to delineate possible interaction of SC keratin with three losartan salts LOS-K, LOS-DEA and LOS-AML salts in addition to AML-BES salt. The results of PCA, combined with comparisons of average second derivative spectra of SC samples treated with these salts and the control SC, showed that LOS-DEA did not interact with SC, thus providing base line permeation of losartan. AML-BES, LOS-AML and LOS-K salts modified the conformational structure of keratin. The disorganization effect on the α-helical structure and induced formation of parallel ß-sheets and random coils were in the order of AML-BESËLOS-AMLËLOS-K. The order of the impact of treatments which resulted in increased formation of ß-turns was AML-BESËLOS-AML. The formation of antiparallel ß-sheets was manifested by LOS-AML. Thus, the overall effect of these salts on the SC protein was AML-BESËLOS-AMLËLOS-K. The impact of LOS-K was associated with improved permeation whereas the impact of LOS-AML was associated with hindered permeation of both losartan and amlodipine. There is a possibility that losartan and amlodipine when present in combination inside SC, their binding to the protein is enhanced leading to being retained within SC.
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Leucemia Mieloide Aguda , Losartán , Humanos , Losartán/farmacología , Sales (Química)/metabolismo , Amlodipino , Preparaciones Farmacéuticas/química , Queratinas/metabolismo , Leucemia Mieloide Aguda/tratamiento farmacológico , Piel/metabolismoRESUMEN
Insulin detemir (IDt) is long-acting insulin whose protraction mechanism is based on a covalently attached fatty acid to an insulin molecule. Utilizing the high affinity of fatty acids towards human serum albumin (HA), the modified detemir molecule binds with good affinity to HA, which functions as a reservoir that leads to a slow and prolonged release of insulin. However, questions were raised over potential interactions between other drugs and IDt through competitive binding on the binding site(s) of HA. In a previous study, concomitant use of esomeprazole (Esom) and erythromycin resulted in severe hypoglycemia, and thus: the drugs including Esom were suggested as enhancers of IDt action through displacing it from its binding site on HA. To further study this possibility, studies utilizing different techniques including, semipermeable membrane dialysis, capillary electrophoresis, UV,NMR spectroscopy, and molecular docking were carried out. Results from various techniques supported the simultaneous binding of Esom along with IDt to HA (i.e., binding in two different sites without signs of competition between the two). Moreover, capillary electrophoresis suggested an increase in the binding affinity of Esom to HA in the presence of IDt (1.9 × 103 Vs 2.7 × 104M-1). Perhaps most interesting was the observation that Esom could bind directly to IDt which was evidenced by all the employed techniques. Direct binding of Esom to IDt, might explain the enhancement in insulin action associated with the concomitant use of Esom. Therefore, Esom might represent a leading insulin-sensitizing compound that might lead to more effective insulin enhancing and less unwanted effects.
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Esomeprazol , Hipoglucemia , Insulina Detemir , Interacciones Farmacológicas , Esomeprazol/efectos adversos , Ácidos Grasos , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemiantes/efectos adversos , Insulina , Insulina Detemir/efectos adversos , Simulación del Acoplamiento Molecular , Albúmina Sérica HumanaRESUMEN
The formation of salts is considered a simple strategy to modify the physicochemical properties of active pharmaceutical ingredients. In this study, seven novel binary and ternary organic salts of ciprofloxacin (CP) were prepared with benzoic acid (BA), acetylsalicylic acid (ASA), p-coumaric acid (PCMA) and p-aminosalicylic acid (PASA). They were characterized by spectroscopic techniques and differential scanning calorimetry. Solubility and partition coefficients values were also measured. Evaluation of the antimicrobial activity of the organic salts against Staphylococcus aureus and Staphylococcus epidermidis revealed that most of the new salts had higher antimicrobial activity than CPHCl against both strains. The most active compounds against S. epidermidis and S. aureus were CP-PASA and CPPCMA, resp., which were up to fourteen times more potent than parent CP-HCl. Our findings indicated a strong correlation between the lipophilicity of the formed salts and their antimicrobial activity and showed that an optimum value of lipophilicity (log P = 0.75) seemed to be necessary to maximize the antimicrobial activity. These findings highlighted the improved physical, thermal and antimicrobial properties of the new salts of CP that can aid in providing higher bioavailability than CP-HCl.
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The focus of this research was to develop and validate a suitable HPLC method, which allows simultaneous determination of three proposed skin model penetrants to investigate the percutaneous diffusion behavior of their combination: caffeine, methyl paraben and butyl paraben. These penetrants were selected because they represent a wide range of lipophilicities. This model highlights the effect of combining penetrants of different molecular properties on their diffusion behavior through skin. The proposed method employed a gradient system that was systematically optimized for separation and quantification of the penetrants. The effect of the stationary phase (C18, C4 and cyano (CN)) was assessed with CN proven to be superior in terms of peak shape, retentivity and dynamic linear range. Significant differences in retention time, peak broadening, and quantifiability between different stationary phases could be demonstrated. The method was validated as per ICH guidelines Q2 (R1) with a satisfactory outcome. The method was successfully applied for real diffusion experiments, and revealed notable differences between the individual penetrants and their ternary mixture on transdermal permeation. The method could potentially be extended to determine these analytes in other related skin permeation investigations.
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Cafeína/análisis , Cromatografía Líquida de Alta Presión/métodos , Parabenos/análisis , Piel/efectos de los fármacos , Administración Cutánea , Cafeína/administración & dosificación , Humanos , Parabenos/administración & dosificación , Absorción Cutánea/efectos de los fármacosRESUMEN
A validated method using capillary electrophoresis was developed, for the determination of orphenadrine citrate in its tablet formulations, in the presence of paracetamol. The method employs a running buffer of 30 mM pentane sulfonate sodium, dissolved in 20 mM MOPS buffer pH 7.7. Samples were injected using hydrodynamic sample injection mode (25 mbar, for 25 s), using positive polarity of 25 kV, at a constant temperature of 30 °C. Samples of orphenadrine citrate alone or in mixture solutions with paracetamol were exposed to various degradation conditions, and were electrophoresed using the recommended condition. The method was found to be specific, linear (r (2) = 0.994), precise, accurate, and robust, with an LOQ of 0.02 mg/mL. The proposed method was successfully applied for measurement of the percentage per label of orphenadrine citrate in commercially available tablets.
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Capillary electrophoresis (CE) method was developed for screening plant extract for potential alpha amylase (AA) inhibitory activity. The method was validated against a well established UV method. Overall, the proposed method was shown able to detect plants with significant alpha amylase inhibitory activity but not those with rather clinically insignificant activities. Fifty plant species were screened using both the proposed CE method and the UV method and seven plant species were found to possess significant AA inhibitory activities. Two plant species were proved to have alpha amylase inhibitory activity for the first time.
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Cinacalcet (CT) is an important drug for the treatment hyperparathyroidism. Only few studies havereported thepotential interaction between CT and other potentially coadministered drugs. In this study, the potential of invitro interaction between CT and DF sodium (DF-Na) was investigated. An ion pair salt of CT with DF was obtained by mixing the two compounds in solution; the product was fully characterized by HPLC analysis, UV, FTIR, NMR spectroscopy in addition to DSC. The solubility and partition coefficients were found to significantly decrease and increase, respectively, for the obtained ion pair salt in comparison to the parent compounds. Dissolution studies in phosphate buffer pH 6.8 revealed a significant decrease in the dissolution of an already poorly water soluble drug (decrease to ~20% of the original). Permeation studies, through Caco-2 cells monolayer, revealed a significant decrease in permeation of CT when coexisted with DF (almost to half). Apparent permeability coefficient (Papp) decreased from 3.6 × 10-6 to 1.8 × 10-6 cm/s. Interestingly, a structure for the formed CT-DF salt that could explain the above findings (increase in lipophilicity), could be proposed based on structural modelling, molecular dynamic simulations and NMR proton chemical shifts analysis.
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Cinacalcet/química , Diclofenaco/química , Modelos Moleculares , Estructura MolecularRESUMEN
Twenty-five structurally diverse compounds have been tested in vitro for their pancreatic lipase (PL) inhibitory activity. Despite the diversity of tested compounds, the relationship comprising structural attributes of the compounds could be established to correlate with the observed inhibitory activity. Compounds that exerted inhibitory action through surface activity were of different profile from the rest of compounds. When co-incubated with orlistat (OsT), important synergistic effects for some compounds (orphenadrine, gliclazide, cefuroxime and sulfacetamide) were revealed, while antagonistic effects were demonstrated for others (camphor sulfonic acid and dinitro salicylic acid). Docking studies for the most active molecules were performed and molecular interaction forces with the PL active site were identified. The results suggested co-binding of OsT along with the other inhibitor in the binding site in cases of synergistic effect but not in the case of antagonistic effect. These results were additionally supported by affinity capillary electrophoresis. In conclusion, synergistic lipase inhibitory activity between OsT and some other pharmaceutical compounds was demonstrated for the first time, which might help improve the pharmacological effect of OsT.
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Inhibidores Enzimáticos/farmacología , Lipasa/antagonistas & inhibidores , Páncreas/metabolismo , Preparaciones Farmacéuticas/química , Animales , Orlistat/farmacología , Relación Estructura-Actividad , PorcinosRESUMEN
This study aims at investigating the potential effect of selected cationic drugs (azithromycin (AZN) and pseudoephedrine sulfate (PSD) on the dissolution profile and intestinal permeation of losartan potassium (LOS) that might occur due to ion pair salt formation. DSC, FT-IR and 1H NMR indicated the formation of ion pair salts between LOS and each of AZN and PSD. Based on NMR chemical shifts calculations, utilizing specialized software, the most likely structures of the salt were proposed and revealed interesting structural features. The obtained ion pair products were shown to have lower aqueous solubilities (water and phosphate buffer pHâ¯6.8) and higher apparent partition coefficient values compared to the parent compound. Neither of the cations affected the dissolution of LOS tablet (Cozaar® 100â¯mg) in the studied media (HCl pHâ¯1.2 and phosphate buffer pHâ¯6.8). Interestingly, AZN significantly increased the dissolution of LOS in phosphate buffer pHâ¯4.5 (f2â¯=â¯33), and an explanation based on distinguished association pattern between AZN and LOS (CH/π) was offered. Employing permeation test across Caco-2 cells monolayer, the apparent permeability coefficient (Papp) of LOS increased significantly (from 0.9â¯×â¯10-5â¯cm/s to 1.8â¯×â¯10-5â¯cm/s) in the presence of the selected cations. Therefore, while the employed cationic drugs were not shown to form ion pair salts under the in-vitro dissolution conditions, they may still participate in significant in-vivo interaction with LOS.
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Azitromicina/química , Losartán/química , Seudoefedrina/química , Azitromicina/farmacocinética , Células CACO-2 , Rastreo Diferencial de Calorimetría , Cationes , Interacciones Farmacológicas , Humanos , Concentración de Iones de Hidrógeno , Losartán/farmacocinética , Espectroscopía de Resonancia Magnética , Permeabilidad , Seudoefedrina/farmacocinética , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Comprimidos/químicaRESUMEN
Levetiracetam (LVT) is a widely used antiepileptic drug (AED). A less invasive sampling method for therapeutic drug monitoring (TDM) would be very useful particularly for children. Saliva has been shown as an adequate sample for TDM of some AEDs. Due to the high hydrophilicity of LVT its separation on common stationary phases is quite a challenge so that previous methods for determination of LVT in saliva employed either gradient high performance liquid chromatographic (HPLC) system or mass spectrometer as a detector. In this study the retention behavior of LVT on some common stationary phases was examined, with C8 being the most retentive. A simple isocratic HPLC method that is based on simple protein precipitation was developed and validated for the determination of LVT in saliva. The method was applied to a sample group of epileptic children for the purpose of assessing potential correlation with plasma LVT levels and to investigate patient's compliance. The results confirmed a reasonable correlation between plasma and salivary levels of LVT (R = 0.9) which supports the use of saliva for TDM of LVT. The study also revealed a significant percentage of epileptic patients having LVT levels below the estimated therapeutic range.
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It has been proposed that Emu oil possesses skin permeation-enhancing effect. This study aimed to address its possible penetration enhancement mechanism(s) using IR microscopy, in accordance with LPP theory. The penetration of Emu oil through the layers of human skin was accomplished by monitoring oil-IR characteristic feature at 3006cm-1. The unsaturated components of Emu oil accumulated at about 270µm depth of skin surface. The interaction of Emu oil with lipid and protein constituents of SC was investigated in comparison with a commonly used enhancer, IPM. Inter-sample spectral differences were identified using PCA and linked with possible enhancement mechanisms. Emu oil treatment caused a change in the slope of the right contour of amide I band of the protein spectral range. This was also clear in the second derivative spectra where the emergence of a new shoulder at higher frequency was evident, suggesting disorganization of keratin α-helix structure. This effect could be a result of disruption of some hydrogen bonds in which amide CO and NH groups of keratin are involved. The low intensity of the emerged shoulder is also in agreement with formation of weaker hydrogen bonds. IPM did not affect the protein component. No conclusions regarding the effect of penetration enhancers on the SC lipids were obtained. This was due to the overlap of the endogenous (skin) and exogenous (oil) CH stretching and scissoring frequencies. The SC carbonyl stretching peak disappeared as a result of IPM treatment which may reflect some degree of lipid extraction.