cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.20038707
title: Formulation and in vitro evaluation of mucoadhesive controlled release matrix tablets of flurbiprofen using response surface methodology

description: The objective of the current study was to formulate mucoadhesive controlled release matrix tablets of flurbiprofen and to optimize its drug release profile and bioadhesion using response surface methodology. Tablets were prepared via a direct compression technique and evaluated for in vitro dissolution parameters and bioadhesive strength. A central composite design for two factors at five levels each was employed for the study. Carbopol 934 and sodium carboxymethylcellulose were taken as independent variables. Fourier transform infrared (FTIR) spectroscopy studies were performed to observe the stability of the drug during direct compression and to check for a drug-polymer interaction. Various kinetic models were applied to evaluate drug release from the polymers. Contour and response surface plots were also drawn to portray the relationship between the independent and response variables. Mucoadhesive tablets of flurbiprofen exhibited non-Fickian drug release kinetics extending towards zero-order, with some formulations (F3, F8, and F9) reaching super case II transport, as the value of the release rate exponent (n) varied between 0.584 and 1.104. Polynomial mathematical models, generated for various response variables, were found to be statistically significant (P&lt;0.05). The study also helped to find the drug's optimum formulation with excellent bioadhesive strength. Suitable combinations of two polymers provided adequate release profile, while carbopol 934 produced more bioadhesion.
DOI: 10.6084/m9.figshare.20038707.v1
title: Formulation and in vitro evaluation of mucoadhesive controlled release matrix tablets of flurbiprofen using response surface methodology

description: The objective of the current study was to formulate mucoadhesive controlled release matrix tablets of flurbiprofen and to optimize its drug release profile and bioadhesion using response surface methodology. Tablets were prepared via a direct compression technique and evaluated for in vitro dissolution parameters and bioadhesive strength. A central composite design for two factors at five levels each was employed for the study. Carbopol 934 and sodium carboxymethylcellulose were taken as independent variables. Fourier transform infrared (FTIR) spectroscopy studies were performed to observe the stability of the drug during direct compression and to check for a drug-polymer interaction. Various kinetic models were applied to evaluate drug release from the polymers. Contour and response surface plots were also drawn to portray the relationship between the independent and response variables. Mucoadhesive tablets of flurbiprofen exhibited non-Fickian drug release kinetics extending towards zero-order, with some formulations (F3, F8, and F9) reaching super case II transport, as the value of the release rate exponent (n) varied between 0.584 and 1.104. Polynomial mathematical models, generated for various response variables, were found to be statistically significant (P&lt;0.05). The study also helped to find the drug's optimum formulation with excellent bioadhesive strength. Suitable combinations of two polymers provided adequate release profile, while carbopol 934 produced more bioadhesion.
DOI: 10.6084/m9.figshare.20038708.v1
title: The effect of dissolution medium, rotation speed and compaction pressure on the intrinsic dissolution rate of amlodipine besylate, using the rotating disk method

description: The aim of this study was to evaluate the effect of dissolution medium, rotation speed and compaction pressure on the intrinsic dissolution rate (IDR) of the antihypertensive drug amlodipine besylate, using the rotating disk method. Accordingly, a fractional factorial design (33-1) was used, employing dissolution media (water, phosphate buffer pH 6.8 and HCl 0.1 M), rotation speed (50, 75 and 100 rpm), and compaction pressure (1000, 1500 and 2000 psi) as independent variables. The assays were randomized and statistically compared using the Statistica(r) 11 software program. Significance testing (ANOVA) indicated that the dissolution medium had a considerable impact on the IDR of amlodipine besylate. Analysis of the linear and quadratic components of the variables led to the proposition of a mathematical model that describes the IDR as a function of the parameters studied. Conversely, the levels of compaction pressure and rotation speed employed during experimental planning were less relevant, especially when the assay was conducted in the HCl 0.1 M medium.
DOI: 10.6084/m9.figshare.20038708
title: The effect of dissolution medium, rotation speed and compaction pressure on the intrinsic dissolution rate of amlodipine besylate, using the rotating disk method

description: The aim of this study was to evaluate the effect of dissolution medium, rotation speed and compaction pressure on the intrinsic dissolution rate (IDR) of the antihypertensive drug amlodipine besylate, using the rotating disk method. Accordingly, a fractional factorial design (33-1) was used, employing dissolution media (water, phosphate buffer pH 6.8 and HCl 0.1 M), rotation speed (50, 75 and 100 rpm), and compaction pressure (1000, 1500 and 2000 psi) as independent variables. The assays were randomized and statistically compared using the Statistica(r) 11 software program. Significance testing (ANOVA) indicated that the dissolution medium had a considerable impact on the IDR of amlodipine besylate. Analysis of the linear and quadratic components of the variables led to the proposition of a mathematical model that describes the IDR as a function of the parameters studied. Conversely, the levels of compaction pressure and rotation speed employed during experimental planning were less relevant, especially when the assay was conducted in the HCl 0.1 M medium.
DOI: 10.6084/m9.figshare.20038711
title: Implementation of vancomycin dosing nomogram in an electronic prescribing system: an innovative tool in antibiotic stewardship

description: Vancomycin (VAN) is the gold standard therapy for Methicillin-resistant Staphylococcus aureus(MRSA) infections such as bacteremia and endocarditis. However, VAN suboptimal dosing for serious infections caused by S. aureus isolates that have elevated minimum inhibitory concentration (MIC), could be associated with poor outcome. Better understanding of VAN pharmacokinetics and pharmacodynamics (PK/PD) has led to the creation of new recommendations with optimized dosing regimens for the treatment of MRSA infections. For severe infectious, such as pneumonia and endocarditis, a VAN serum trough concentration of 15-20 mg/L at the steady state should be targeted. The aim of this study was to show how a nomogram with updated VAN dosing was devised and how it was implemented in the electronic prescribing (e-prescribing) system of a teaching hospital. VAN loading dose and maintenance doses were calculated from a pharmacokinetic equation using basic parameters: weight, estimated creatinine clearance, as well as peak and trough serum concentrations. The implementation of the VAN dosing nomogram in the hospital e-prescribing system definitively changed the long-standing medical prescription fallacy of "same dose fits all". Finally, this computer-based electronic program has allowed a wide-ranging intervention and should be recognized as a powerful tool for implementation in antimicrobial stewardship programs.
DOI: 10.6084/m9.figshare.20038711.v1
title: Implementation of vancomycin dosing nomogram in an electronic prescribing system: an innovative tool in antibiotic stewardship

description: Vancomycin (VAN) is the gold standard therapy for Methicillin-resistant Staphylococcus aureus(MRSA) infections such as bacteremia and endocarditis. However, VAN suboptimal dosing for serious infections caused by S. aureus isolates that have elevated minimum inhibitory concentration (MIC), could be associated with poor outcome. Better understanding of VAN pharmacokinetics and pharmacodynamics (PK/PD) has led to the creation of new recommendations with optimized dosing regimens for the treatment of MRSA infections. For severe infectious, such as pneumonia and endocarditis, a VAN serum trough concentration of 15-20 mg/L at the steady state should be targeted. The aim of this study was to show how a nomogram with updated VAN dosing was devised and how it was implemented in the electronic prescribing (e-prescribing) system of a teaching hospital. VAN loading dose and maintenance doses were calculated from a pharmacokinetic equation using basic parameters: weight, estimated creatinine clearance, as well as peak and trough serum concentrations. The implementation of the VAN dosing nomogram in the hospital e-prescribing system definitively changed the long-standing medical prescription fallacy of "same dose fits all". Finally, this computer-based electronic program has allowed a wide-ranging intervention and should be recognized as a powerful tool for implementation in antimicrobial stewardship programs.
DOI: 10.6084/m9.figshare.20038716
title: Use of solid dispersions to increase stability of dithranol in topical formulations

description: The present study was planned to improve the stability of dithranol using solid dispersions (SD). Two different SD at a 1:9 ratio of dithranol/excipient were prepared: one of them using glyceryl behenate as excipient and the other using a mixture of argan oil with stearic acid (1:8 ratio) as excipient. Pure dithranol and SD of dithranol were incorporated in an oil-in-water cream and in a hydrophobic ointment in a drug/dermatological base ratio of 1:10. The physical and mechanical properties of semisolid formulations incorporating the pure drug and the developed SD were evaluated through rheological and textural analysis. To evaluate the stability, L*a*b* color space parameters of SD and semisolid formulations, and pH of hydrophilic formulations were determined at defined times, during one month. Each sample was stored at different conditions namely, light exposure (room temperature), high temperature exposition (37 °C) (protected from light) and protected from light (room temperature). Despite higher values of firmness and adhesiveness, hydrophobic ointment exhibited the best rheological features compared to the oil-in-water cream, namely a shear-thinning behavior and high thixotropy. These formulations have also presented more stability, with minor changes in L*a*b* color space parameters. The results of this study indicate that is possible to conclude that the developed SD contributed to the increased stability of dithranol.
DOI: 10.6084/m9.figshare.20038716.v1
title: Use of solid dispersions to increase stability of dithranol in topical formulations

description: The present study was planned to improve the stability of dithranol using solid dispersions (SD). Two different SD at a 1:9 ratio of dithranol/excipient were prepared: one of them using glyceryl behenate as excipient and the other using a mixture of argan oil with stearic acid (1:8 ratio) as excipient. Pure dithranol and SD of dithranol were incorporated in an oil-in-water cream and in a hydrophobic ointment in a drug/dermatological base ratio of 1:10. The physical and mechanical properties of semisolid formulations incorporating the pure drug and the developed SD were evaluated through rheological and textural analysis. To evaluate the stability, L*a*b* color space parameters of SD and semisolid formulations, and pH of hydrophilic formulations were determined at defined times, during one month. Each sample was stored at different conditions namely, light exposure (room temperature), high temperature exposition (37 °C) (protected from light) and protected from light (room temperature). Despite higher values of firmness and adhesiveness, hydrophobic ointment exhibited the best rheological features compared to the oil-in-water cream, namely a shear-thinning behavior and high thixotropy. These formulations have also presented more stability, with minor changes in L*a*b* color space parameters. The results of this study indicate that is possible to conclude that the developed SD contributed to the increased stability of dithranol.
DOI: 10.6084/m9.figshare.20038717
title: Development and validation of a simple spectrophotometric method for the determination of methyldopa in both bulk and marketed dosage formulations

description: A simple, precise, sensitive, rapid, specific and economical spectrophotometric method was developed to determine methyldopa (MTD) content in bulk and pharmaceutical dosage formulations. The proposed method was based on the formation of a colored product from the nitrosation reaction of MTD with sodium nitrite in an acid medium. The resultant nitroso derivative species reacts further with sodium hydroxide and is converted it into a more stable compound. This yellow nitrosation product exhibited an absorption maximum at 430 nm. Beer's Law was obeyed in a concentration range of 6.37 to 82.81 μg mL-1 MTD with an excellent coefficient of determination (R2 = 0.9998). No interference was observed from common excipients in formulations. The results showed the method to be simple, accurate and readily applied for the determination of MTD in pure form and in pharmaceutical preparations. The analytical results obtained for these products using the proposed method are in agreement with those of the Brazilian Pharmacopoeia procedure at a 95% confidence level.
DOI: 10.6084/m9.figshare.20038717.v1
title: Development and validation of a simple spectrophotometric method for the determination of methyldopa in both bulk and marketed dosage formulations

description: A simple, precise, sensitive, rapid, specific and economical spectrophotometric method was developed to determine methyldopa (MTD) content in bulk and pharmaceutical dosage formulations. The proposed method was based on the formation of a colored product from the nitrosation reaction of MTD with sodium nitrite in an acid medium. The resultant nitroso derivative species reacts further with sodium hydroxide and is converted it into a more stable compound. This yellow nitrosation product exhibited an absorption maximum at 430 nm. Beer's Law was obeyed in a concentration range of 6.37 to 82.81 μg mL-1 MTD with an excellent coefficient of determination (R2 = 0.9998). No interference was observed from common excipients in formulations. The results showed the method to be simple, accurate and readily applied for the determination of MTD in pure form and in pharmaceutical preparations. The analytical results obtained for these products using the proposed method are in agreement with those of the Brazilian Pharmacopoeia procedure at a 95% confidence level.
DOI: 10.6084/m9.figshare.20038723.v1
title: Anti-inflammatory, analgesic, and immunostimulatory effects of Luehea divaricata Mart. & Zucc. (Malvaceae) bark

description: Luehea divaricata (Malvaceae) is a plant widely used for treatment of various inflammatory and infectious conditions; however few reports discuss its biological properties. The aim of this study was to evaluate the anti-inflammatory and analgesic effects as well as the macrophage activity in mice treated with the hydroalcoholic crude extract of L. divaricata(CLD). Thin layer chromatography revealed presence of epicathequin, stigmasterol, lupeol and α,β-amyrin in the extract. To evaluate the anti-inflammatory and analgesic activities, animals were subjected to paw edema induced by carrageenan test, writhing, formalin and capsaicin tests. Immunomodulatory activity was evaluated by adhesion and phagocytic capacity, lysosomal volume, and reactive oxygen species (ROS) production by peritoneal macrophages, after daily treatment with CLD for 15 days. CLD promoted reduction in paw edema (36.8% and 50.2%; p&lt;0.05 at doses of 100 and 300 mg/kg, respectively), inhibited writhing behavior at the higher dose (64.4%, p&lt;0.05), reduced formalin reactivity (81.2% and 91.6% at doses of 100 and 300 mg/kg, respectively, p&lt;0.05), and reduced capsaicin reactivity by 63.9% (300 mg/kg). CLD (200 mg• kg-1• day-1) increased phagocytosis capacity of macrophages (~3 fold, p&lt;0.05), neutral red uptake (~50%, p&lt;0.001), and ROS production (~90%, p&lt;0.001). These data suggest that CLD possesses anti-inflammatory, analgesic and immunostimulatory properties.
DOI: 10.6084/m9.figshare.20038723
title: Anti-inflammatory, analgesic, and immunostimulatory effects of Luehea divaricata Mart. & Zucc. (Malvaceae) bark

description: Luehea divaricata (Malvaceae) is a plant widely used for treatment of various inflammatory and infectious conditions; however few reports discuss its biological properties. The aim of this study was to evaluate the anti-inflammatory and analgesic effects as well as the macrophage activity in mice treated with the hydroalcoholic crude extract of L. divaricata(CLD). Thin layer chromatography revealed presence of epicathequin, stigmasterol, lupeol and α,β-amyrin in the extract. To evaluate the anti-inflammatory and analgesic activities, animals were subjected to paw edema induced by carrageenan test, writhing, formalin and capsaicin tests. Immunomodulatory activity was evaluated by adhesion and phagocytic capacity, lysosomal volume, and reactive oxygen species (ROS) production by peritoneal macrophages, after daily treatment with CLD for 15 days. CLD promoted reduction in paw edema (36.8% and 50.2%; p&lt;0.05 at doses of 100 and 300 mg/kg, respectively), inhibited writhing behavior at the higher dose (64.4%, p&lt;0.05), reduced formalin reactivity (81.2% and 91.6% at doses of 100 and 300 mg/kg, respectively, p&lt;0.05), and reduced capsaicin reactivity by 63.9% (300 mg/kg). CLD (200 mg• kg-1• day-1) increased phagocytosis capacity of macrophages (~3 fold, p&lt;0.05), neutral red uptake (~50%, p&lt;0.001), and ROS production (~90%, p&lt;0.001). These data suggest that CLD possesses anti-inflammatory, analgesic and immunostimulatory properties.
DOI: 10.6084/m9.figshare.20038725.v1
title: Optimization of a spectrofluorimetric method based on a central composite design for the determination of potassium losartan in pharmaceutical products

description: Here, a spectrofluorimetric method for the determination of potassium losartan (PL) in pharmaceutical products is described. The effects of critical parameters, pH, acid molarity, and temperature, on the fluorescence intensity of PL were analyzed, and these parameters were optimized using a central composite design (CCD). The highest fluorescent intensity at excitation (λex) and emission (λem) wavelengths of 248 nm and 410 nm, respectively, was achieved using 0.01 M sulfurous acid (pH 2) at 21.6 °C. Under optimum conditions, the method was linear from 0.025-0.5 µg/mL, with a reasonably high correlation coefficient (0.9993). Furthermore, the method was very sensitive (LOQ, 0.006), accurate (RE, ≤7.06), and precise (%RSD, ≤6.51). After development and validation of the method, samples containing PL were analyzed with this method, and the obtained data were statistically compared with those obtained with a previously published reference method using a two one-sided equivalence test (TOST). According to the data, the results from the proposed and reference assays were equivalent.
DOI: 10.6084/m9.figshare.20038725
title: Optimization of a spectrofluorimetric method based on a central composite design for the determination of potassium losartan in pharmaceutical products

description: Here, a spectrofluorimetric method for the determination of potassium losartan (PL) in pharmaceutical products is described. The effects of critical parameters, pH, acid molarity, and temperature, on the fluorescence intensity of PL were analyzed, and these parameters were optimized using a central composite design (CCD). The highest fluorescent intensity at excitation (λex) and emission (λem) wavelengths of 248 nm and 410 nm, respectively, was achieved using 0.01 M sulfurous acid (pH 2) at 21.6 °C. Under optimum conditions, the method was linear from 0.025-0.5 µg/mL, with a reasonably high correlation coefficient (0.9993). Furthermore, the method was very sensitive (LOQ, 0.006), accurate (RE, ≤7.06), and precise (%RSD, ≤6.51). After development and validation of the method, samples containing PL were analyzed with this method, and the obtained data were statistically compared with those obtained with a previously published reference method using a two one-sided equivalence test (TOST). According to the data, the results from the proposed and reference assays were equivalent.
DOI: 10.6084/m9.figshare.20038729.v1
title: Standardization method for measurement of hydroxyurea by Ultra High Efficiency Liquid Chromatography in plasma of patients with sickle cell disease

description: Sickle cell anemia (SCA) is a recessively inherited disease characterized by chronic hemolytic anemia, chronic inflammation, and acute episodes of hemolysis. Hydroxyurea (HU) is widely used to increase the levels of fetal hemoglobin (HbF). The objective of this study was to standardize and validate a method for the quantification of HU in human plasma by using ultra high performance liquid chromatography (UPLC) in order to determine the plasma HU levels in adult patients with SCA who had been treated with HU. We used an analytical reverse phase column (Nucleosil C18) with a mobile phase consisting of acetonitrile/water (16.7/83.3). The retention times of HU, urea, and methylurea were 6.7, 7.7, and 11.4 min, respectively. All parameters of the validation process were defined. To determine the precision and accuracy of quality controls, HU in plasma was used at concentrations of 100, 740, and 1600 µM, with methylurea as the internal standard. Linearity was assessed in the range of 50-1600 µM HU in plasma, obtaining a correlation coefficient of 0.99. The method was accurate and precise and can be used for the quantitative determination of HU for therapeutic monitoring of patients with SCA treated with HU.
DOI: 10.6084/m9.figshare.20038729
title: Standardization method for measurement of hydroxyurea by Ultra High Efficiency Liquid Chromatography in plasma of patients with sickle cell disease

description: Sickle cell anemia (SCA) is a recessively inherited disease characterized by chronic hemolytic anemia, chronic inflammation, and acute episodes of hemolysis. Hydroxyurea (HU) is widely used to increase the levels of fetal hemoglobin (HbF). The objective of this study was to standardize and validate a method for the quantification of HU in human plasma by using ultra high performance liquid chromatography (UPLC) in order to determine the plasma HU levels in adult patients with SCA who had been treated with HU. We used an analytical reverse phase column (Nucleosil C18) with a mobile phase consisting of acetonitrile/water (16.7/83.3). The retention times of HU, urea, and methylurea were 6.7, 7.7, and 11.4 min, respectively. All parameters of the validation process were defined. To determine the precision and accuracy of quality controls, HU in plasma was used at concentrations of 100, 740, and 1600 µM, with methylurea as the internal standard. Linearity was assessed in the range of 50-1600 µM HU in plasma, obtaining a correlation coefficient of 0.99. The method was accurate and precise and can be used for the quantitative determination of HU for therapeutic monitoring of patients with SCA treated with HU.